[{"scopus_import":"1","has_accepted_license":"1","article_processing_charge":"No","day":"18","article_type":"original","citation":{"ista":"Stefanescu C, Van Gogh M, Roblek M, Heikenwalder M, Borsig L. 2021. TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms. Frontiers in Oncology. 11, 765151.","ieee":"C. Stefanescu, M. Van Gogh, M. Roblek, M. Heikenwalder, and L. Borsig, “TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms,” Frontiers in Oncology, vol. 11. Frontiers, 2021.","apa":"Stefanescu, C., Van Gogh, M., Roblek, M., Heikenwalder, M., & Borsig, L. (2021). TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms. Frontiers in Oncology. Frontiers. https://doi.org/10.3389/fonc.2021.765151","ama":"Stefanescu C, Van Gogh M, Roblek M, Heikenwalder M, Borsig L. TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms. Frontiers in Oncology. 2021;11. doi:10.3389/fonc.2021.765151","chicago":"Stefanescu, Cristina, Merel Van Gogh, Marko Roblek, Mathias Heikenwalder, and Lubor Borsig. “TGFβ Signaling in Myeloid Cells Promotes Lung and Liver Metastasis through Different Mechanisms.” Frontiers in Oncology. Frontiers, 2021. https://doi.org/10.3389/fonc.2021.765151.","mla":"Stefanescu, Cristina, et al. “TGFβ Signaling in Myeloid Cells Promotes Lung and Liver Metastasis through Different Mechanisms.” Frontiers in Oncology, vol. 11, 765151, Frontiers, 2021, doi:10.3389/fonc.2021.765151.","short":"C. Stefanescu, M. Van Gogh, M. Roblek, M. Heikenwalder, L. Borsig, Frontiers in Oncology 11 (2021)."},"publication":"Frontiers in Oncology","date_published":"2021-11-18T00:00:00Z","type":"journal_article","abstract":[{"lang":"eng","text":"TGFβ overexpression is commonly detected in cancer patients and correlates with poor prognosis and metastasis. Cancer progression is often associated with an enhanced recruitment of myeloid-derived cells to the tumor microenvironment. Here we show that functional TGFβ-signaling in myeloid cells is required for metastasis to the lungs and the liver. Myeloid-specific deletion of Tgfbr2 resulted in reduced spontaneous lung metastasis, which was associated with a reduction of proinflammatory cytokines in the metastatic microenvironment. Notably, CD8+ T cell depletion in myeloid-specific Tgfbr2-deficient mice rescued lung metastasis. Myeloid-specific Tgfbr2-deficiency resulted in reduced liver metastasis with an almost complete absence of myeloid cells within metastatic foci. On contrary, an accumulation of Tgfβ-responsive myeloid cells was associated with an increased recruitment of monocytes and granulocytes and higher proinflammatory cytokine levels in control mice. Monocytic cells isolated from metastatic livers of Tgfbr2-deficient mice showed increased polarization towards the M1 phenotype, Tnfα and Il-1β expression, reduced levels of M2 markers and reduced production of chemokines responsible for myeloid-cell recruitment. No significant differences in Tgfβ levels were observed at metastatic sites of any model. These data demonstrate that Tgfβ signaling in monocytic myeloid cells suppresses CD8+ T cell activity during lung metastasis, while these cells actively contribute to tumor growth during liver metastasis. Thus, myeloid cells modulate metastasis through different mechanisms in a tissue-specific manner."}],"intvolume":" 11","title":"TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms","ddc":["610"],"status":"public","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"10536","oa_version":"Published Version","file":[{"file_id":"10539","relation":"main_file","date_updated":"2021-12-13T13:32:37Z","date_created":"2021-12-13T13:32:37Z","success":1,"checksum":"56cbac80e6891ce750511a30161b7792","file_name":"2021_Frontiers_Stefanescu.pdf","access_level":"open_access","creator":"alisjak","content_type":"application/pdf","file_size":9245199}],"publication_identifier":{"eissn":["2234-943X"]},"month":"11","isi":1,"quality_controlled":"1","oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"pmid":["34868988"],"isi":["000726603400001"]},"language":[{"iso":"eng"}],"doi":"10.3389/fonc.2021.765151","article_number":"765151","file_date_updated":"2021-12-13T13:32:37Z","department":[{"_id":"DaSi"}],"publisher":"Frontiers","publication_status":"published","pmid":1,"acknowledgement":"The authors acknowledge the assistance of the Laboratory Animal Services Center (LASC) – UZH, Center for Microscopy and Image Analysis, and the Flow Cytometry Center of the University of Zurich.","year":"2021","volume":11,"date_created":"2021-12-12T23:01:27Z","date_updated":"2023-08-17T06:20:32Z","author":[{"full_name":"Stefanescu, Cristina","last_name":"Stefanescu","first_name":"Cristina"},{"full_name":"Van Gogh, Merel","first_name":"Merel","last_name":"Van Gogh"},{"id":"3047D808-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9588-1389","first_name":"Marko","last_name":"Roblek","full_name":"Roblek, Marko"},{"first_name":"Mathias","last_name":"Heikenwalder","full_name":"Heikenwalder, Mathias"},{"full_name":"Borsig, Lubor","first_name":"Lubor","last_name":"Borsig"}]},{"type":"journal_article","abstract":[{"text":"Unpaired ligands are secreted signals that act via a GP130-like receptor, domeless, to activate JAK/STAT signalling in Drosophila. Like many mammalian cytokines, unpaireds can be activated by infection and other stresses and can promote insulin resistance in target tissues. However, the importance of this effect in non-inflammatory physiology is unknown. Here, we identify a requirement for unpaired-JAK signalling as a metabolic regulator in healthy adult Drosophila muscle. Adult muscles show basal JAK-STAT signalling activity in the absence of any immune challenge. Plasmatocytes (Drosophila macrophages) are an important source of this tonic signal. Loss of the dome receptor on adult muscles significantly reduces lifespan and causes local and systemic metabolic pathology. These pathologies result from hyperactivation of AKT and consequent deregulation of metabolism. Thus, we identify a cytokine signal that must be received in muscle to control AKT activity and metabolic homeostasis.","lang":"eng"}],"_id":"7466","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","intvolume":" 9","status":"public","title":"Muscle function and homeostasis require cytokine inhibition of AKT activity in Drosophila","ddc":["570"],"file":[{"relation":"main_file","file_id":"7470","date_created":"2020-02-10T08:53:16Z","date_updated":"2020-07-14T12:47:59Z","checksum":"3a072be843f416c7a7d532a51dc0addb","file_name":"2020_eLife_Kierdorf.pdf","access_level":"open_access","file_size":4959933,"content_type":"application/pdf","creator":"dernst"}],"oa_version":"Published Version","scopus_import":"1","has_accepted_license":"1","article_processing_charge":"No","day":"20","citation":{"ama":"Kierdorf K, Hersperger F, Sharrock J, et al. Muscle function and homeostasis require cytokine inhibition of AKT activity in Drosophila. eLife. 2020;9. doi:10.7554/eLife.51595","ista":"Kierdorf K, Hersperger F, Sharrock J, Vincent CM, Ustaoglu P, Dou J, György A, Groß O, Siekhaus DE, Dionne MS. 2020. Muscle function and homeostasis require cytokine inhibition of AKT activity in Drosophila. eLife. 9, e51595.","ieee":"K. Kierdorf et al., “Muscle function and homeostasis require cytokine inhibition of AKT activity in Drosophila,” eLife, vol. 9. eLife Sciences Publications, 2020.","apa":"Kierdorf, K., Hersperger, F., Sharrock, J., Vincent, C. M., Ustaoglu, P., Dou, J., … Dionne, M. S. (2020). Muscle function and homeostasis require cytokine inhibition of AKT activity in Drosophila. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.51595","mla":"Kierdorf, Katrin, et al. “Muscle Function and Homeostasis Require Cytokine Inhibition of AKT Activity in Drosophila.” ELife, vol. 9, e51595, eLife Sciences Publications, 2020, doi:10.7554/eLife.51595.","short":"K. Kierdorf, F. Hersperger, J. Sharrock, C.M. Vincent, P. Ustaoglu, J. Dou, A. György, O. Groß, D.E. Siekhaus, M.S. Dionne, ELife 9 (2020).","chicago":"Kierdorf, Katrin, Fabian Hersperger, Jessica Sharrock, Crystal M. Vincent, Pinar Ustaoglu, Jiawen Dou, Attila György, Olaf Groß, Daria E Siekhaus, and Marc S. Dionne. “Muscle Function and Homeostasis Require Cytokine Inhibition of AKT Activity in Drosophila.” ELife. eLife Sciences Publications, 2020. https://doi.org/10.7554/eLife.51595."},"publication":"eLife","article_type":"original","date_published":"2020-01-20T00:00:00Z","article_number":"e51595","file_date_updated":"2020-07-14T12:47:59Z","year":"2020","publisher":"eLife Sciences Publications","department":[{"_id":"DaSi"}],"publication_status":"published","author":[{"full_name":"Kierdorf, Katrin","last_name":"Kierdorf","first_name":"Katrin"},{"first_name":"Fabian","last_name":"Hersperger","full_name":"Hersperger, Fabian"},{"last_name":"Sharrock","first_name":"Jessica","full_name":"Sharrock, Jessica"},{"full_name":"Vincent, Crystal M.","last_name":"Vincent","first_name":"Crystal M."},{"first_name":"Pinar","last_name":"Ustaoglu","full_name":"Ustaoglu, Pinar"},{"full_name":"Dou, Jiawen","last_name":"Dou","first_name":"Jiawen"},{"full_name":"György, Attila","first_name":"Attila","last_name":"György","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1819-198X"},{"first_name":"Olaf","last_name":"Groß","full_name":"Groß, Olaf"},{"first_name":"Daria E","last_name":"Siekhaus","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8323-8353","full_name":"Siekhaus, Daria E"},{"last_name":"Dionne","first_name":"Marc S.","full_name":"Dionne, Marc S."}],"volume":9,"date_created":"2020-02-09T23:00:51Z","date_updated":"2023-08-17T14:36:39Z","publication_identifier":{"eissn":["2050084X"]},"month":"01","external_id":{"isi":["000512304800001"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"project":[{"_id":"253B6E48-B435-11E9-9278-68D0E5697425","grant_number":"P29638","name":"Drosophila TNFa´s Funktion in Immunzellen","call_identifier":"FWF"}],"quality_controlled":"1","isi":1,"doi":"10.7554/eLife.51595","language":[{"iso":"eng"}]},{"date_published":"2020-12-30T00:00:00Z","page":"141","citation":{"chicago":"Emtenani, Shamsi. “Metabolic Regulation of Drosophila Macrophage Tissue Invasion.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8983.","short":"S. Emtenani, Metabolic Regulation of Drosophila Macrophage Tissue Invasion, Institute of Science and Technology Austria, 2020.","mla":"Emtenani, Shamsi. Metabolic Regulation of Drosophila Macrophage Tissue Invasion. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8983.","apa":"Emtenani, S. (2020). Metabolic regulation of Drosophila macrophage tissue invasion. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8983","ieee":"S. Emtenani, “Metabolic regulation of Drosophila macrophage tissue invasion,” Institute of Science and Technology Austria, 2020.","ista":"Emtenani S. 2020. Metabolic regulation of Drosophila macrophage tissue invasion. Institute of Science and Technology Austria.","ama":"Emtenani S. Metabolic regulation of Drosophila macrophage tissue invasion. 2020. doi:10.15479/AT:ISTA:8983"},"day":"30","has_accepted_license":"1","article_processing_charge":"No","oa_version":"Published Version","file":[{"embargo":"2021-12-30","file_id":"8984","relation":"main_file","checksum":"ec2797ab7a6f253b35df0572b36d1b43","date_updated":"2021-12-31T23:30:04Z","date_created":"2020-12-30T15:34:01Z","access_level":"open_access","file_name":"Thesis_Shamsi_Emtenani_pdfA.pdf","creator":"semtenan","file_size":10848175,"content_type":"application/pdf"},{"file_name":"Thesis_Shamsi_Emtenani_source file.pdf","embargo_to":"open_access","access_level":"closed","creator":"semtenan","file_size":10073648,"content_type":"application/pdf","file_id":"8985","relation":"source_file","date_updated":"2021-12-31T23:30:04Z","date_created":"2020-12-30T15:37:36Z","checksum":"cc30e6608a9815414024cf548dff3b3a"}],"title":"Metabolic regulation of Drosophila macrophage tissue invasion","ddc":["570"],"status":"public","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"8983","abstract":[{"lang":"eng","text":"Metabolic adaptation is a critical feature of migrating cells. It tunes the metabolic programs of migrating cells to allow them to efficiently exert their crucial roles in development, inflammatory responses and tumor metastasis. Cell migration through physically challenging contexts requires energy. However, how the metabolic reprogramming that underlies in vivo cell invasion is controlled is still unanswered. In my PhD project, I identify a novel conserved metabolic shift in Drosophila melanogaster immune cells that by modulating their bioenergetic potential controls developmentally programmed tissue invasion. We show that this regulation requires a novel conserved nuclear protein, named Atossa. Atossa enhances the transcription of a set of proteins, including an RNA helicase Porthos and two metabolic enzymes, each of which increases the tissue invasion of leading Drosophila macrophages and can rescue the atossa mutant phenotype. Porthos selectively regulates the translational efficiency of a subset of mRNAs containing a 5’-UTR cis-regulatory TOP-like sequence. These 5’TOPL mRNA targets encode mitochondrial-related proteins, including subunits of mitochondrial oxidative phosphorylation (OXPHOS) components III and V and other metabolic-related proteins. Porthos powers up mitochondrial OXPHOS to engender a sufficient ATP supply, which is required for tissue invasion of leading macrophages. Atossa’s two vertebrate orthologs rescue the invasion defect. In my PhD project, I elucidate that Atossa displays a conserved developmental metabolic control to modulate metabolic capacities and the cellular energy state, through altered transcription and translation, to aid the tissue infiltration of leading cells into energy demanding barriers."}],"alternative_title":["ISTA Thesis"],"type":"dissertation","degree_awarded":"PhD","supervisor":[{"full_name":"Siekhaus, Daria E","last_name":"Siekhaus","first_name":"Daria E","orcid":"0000-0001-8323-8353","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"E-Lib"},{"_id":"CampIT"}],"language":[{"iso":"eng"}],"doi":"10.15479/AT:ISTA:8983","oa":1,"month":"12","publication_identifier":{"issn":["2663-337X"]},"date_created":"2020-12-30T15:41:26Z","date_updated":"2023-09-07T13:24:17Z","author":[{"last_name":"Emtenani","first_name":"Shamsi","orcid":"0000-0001-6981-6938","id":"49D32318-F248-11E8-B48F-1D18A9856A87","full_name":"Emtenani, Shamsi"}],"related_material":{"record":[{"id":"8557","status":"public","relation":"part_of_dissertation"},{"relation":"part_of_dissertation","status":"public","id":"6187"}]},"publication_status":"published","department":[{"_id":"DaSi"}],"publisher":"Institute of Science and Technology Austria","year":"2020","acknowledgement":"Also, I would like to express my appreciation and thanks to the Bioimaging facility, LSF, GSO, library, and IT people at IST Austria.","file_date_updated":"2021-12-31T23:30:04Z"},{"department":[{"_id":"DaSi"},{"_id":"JoCs"}],"publication_status":"submitted","status":"public","title":"Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance","acknowledgement":"We thank the following for their contributions: The Drosophila Genomics Resource Center supported by NIH grant 2P40OD010949-10A1 for plasmids, K. Brueckner. B. Stramer, M. Uhlirova, O. Schuldiner, the Bloomington Drosophila Stock Center supported by NIH grant P40OD018537 and the Vienna Drosophila Resource Center for fly stocks, FlyBase (Thurmond et al., 2019) for essential genomic information, and the BDGP in situ database for data (Tomancak et al., 2002, 2007). For antibodies, we thank the Developmental Studies Hybridoma Bank, which was created by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the NIH, and is maintained at the University of Iowa, as well as J. Zeitlinger for her generous gift of Dfos antibody. We thank the Vienna BioCenter Core Facilities for RNA sequencing and analysis and the Life Scientific Service Units at IST Austria for technical support and assistance with microscopy and FACS analysis. We thank C.P. Heisenberg, P. Martin, M. Sixt and Siekhaus group members for discussions and T.Hurd, A. Ratheesh and P. Rangan for comments on the manuscript. A.G. was supported by the Austrian Science Fund (FWF) grant DASI_FWF01_P29638S, D.E.S. by Marie Curie CIG 334077/IRTIM. M.S. is supported by the FWF, PhD program W1212 915 and the European Research Council (ERC) Advanced grant (ERC-2015-AdG TNT-Tumors 694883). S.W. is supported by an OEAW, DOC fellowship.","_id":"8557","year":"2020","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Preprint","date_updated":"2024-03-28T23:30:25Z","date_created":"2020-09-23T09:36:47Z","related_material":{"record":[{"relation":"later_version","status":"public","id":"10614"},{"id":"8983","relation":"dissertation_contains","status":"public"}]},"author":[{"id":"47F080FE-F248-11E8-B48F-1D18A9856A87","first_name":"Vera","last_name":"Belyaeva","full_name":"Belyaeva, Vera"},{"full_name":"Wachner, Stephanie","id":"2A95E7B0-F248-11E8-B48F-1D18A9856A87","last_name":"Wachner","first_name":"Stephanie"},{"full_name":"Gridchyn, Igor","id":"4B60654C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1807-1929","first_name":"Igor","last_name":"Gridchyn"},{"full_name":"Linder, Markus","last_name":"Linder","first_name":"Markus"},{"full_name":"Emtenani, Shamsi","orcid":"0000-0001-6981-6938","id":"49D32318-F248-11E8-B48F-1D18A9856A87","last_name":"Emtenani","first_name":"Shamsi"},{"full_name":"György, Attila","first_name":"Attila","last_name":"György","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-1819-198X"},{"full_name":"Sibilia, Maria","first_name":"Maria","last_name":"Sibilia"},{"orcid":"0000-0001-8323-8353","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","last_name":"Siekhaus","first_name":"Daria E","full_name":"Siekhaus, Daria E"}],"type":"preprint","ec_funded":1,"abstract":[{"lang":"eng","text":"The infiltration of immune cells into tissues underlies the establishment of tissue resident macrophages, and responses to infections and tumors. Yet the mechanisms immune cells utilize to negotiate tissue barriers in living organisms are not well understood, and a role for cortical actin has not been examined. Here we find that the tissue invasion of Drosophila macrophages, also known as plasmatocytes or hemocytes, utilizes enhanced cortical F-actin levels stimulated by the Drosophila member of the fos proto oncogene transcription factor family (Dfos, Kayak). RNA sequencing analysis and live imaging show that Dfos enhances F-actin levels around the entire macrophage surface by increasing mRNA levels of the membrane spanning molecular scaffold tetraspanin TM4SF, and the actin cross-linking filamin Cheerio which are themselves required for invasion. Cortical F-actin levels are critical as expressing a dominant active form of Diaphanous, a actin polymerizing Formin, can rescue the Dfos Dominant Negative macrophage invasion defect. In vivo imaging shows that Dfos is required to enhance the efficiency of the initial phases of macrophage tissue entry. Genetic evidence argues that this Dfos-induced program in macrophages counteracts the constraint produced by the tension of surrounding tissues and buffers the mechanical properties of the macrophage nucleus from affecting tissue entry. We thus identify tuning the cortical actin cytoskeleton through Dfos as a key process allowing efficient forward movement of an immune cell into surrounding tissues."}],"project":[{"name":"Drosophila TNFa´s Funktion in Immunzellen","call_identifier":"FWF","grant_number":"P29638","_id":"253B6E48-B435-11E9-9278-68D0E5697425"},{"name":"Investigating the role of transporters in invasive migration through junctions","call_identifier":"FP7","_id":"2536F660-B435-11E9-9278-68D0E5697425","grant_number":"334077"},{"grant_number":"24800","_id":"26199CA4-B435-11E9-9278-68D0E5697425","name":"Tissue barrier penetration is crucial for immunity and metastasis"}],"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2020.09.18.301481"}],"citation":{"chicago":"Belyaeva, Vera, Stephanie Wachner, Igor Gridchyn, Markus Linder, Shamsi Emtenani, Attila György, Maria Sibilia, and Daria E Siekhaus. “Cortical Actin Properties Controlled by Drosophila Fos Aid Macrophage Infiltration against Surrounding Tissue Resistance.” BioRxiv, n.d. https://doi.org/10.1101/2020.09.18.301481.","mla":"Belyaeva, Vera, et al. “Cortical Actin Properties Controlled by Drosophila Fos Aid Macrophage Infiltration against Surrounding Tissue Resistance.” BioRxiv, doi:10.1101/2020.09.18.301481.","short":"V. Belyaeva, S. Wachner, I. Gridchyn, M. Linder, S. Emtenani, A. György, M. Sibilia, D.E. Siekhaus, BioRxiv (n.d.).","ista":"Belyaeva V, Wachner S, Gridchyn I, Linder M, Emtenani S, György A, Sibilia M, Siekhaus DE. Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance. bioRxiv, 10.1101/2020.09.18.301481.","apa":"Belyaeva, V., Wachner, S., Gridchyn, I., Linder, M., Emtenani, S., György, A., … Siekhaus, D. E. (n.d.). Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance. bioRxiv. https://doi.org/10.1101/2020.09.18.301481","ieee":"V. Belyaeva et al., “Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance,” bioRxiv. .","ama":"Belyaeva V, Wachner S, Gridchyn I, et al. Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance. bioRxiv. doi:10.1101/2020.09.18.301481"},"oa":1,"publication":"bioRxiv","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"LifeSc"}],"doi":"10.1101/2020.09.18.301481","date_published":"2020-09-18T00:00:00Z","article_processing_charge":"No","day":"18","month":"09"},{"pmid":1,"year":"2019","publisher":"AACR","department":[{"_id":"DaSi"}],"publication_status":"published","author":[{"full_name":"Roblek, Marko","first_name":"Marko","last_name":"Roblek","id":"3047D808-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9588-1389"},{"full_name":"Protsyuk, Darya","first_name":"Darya","last_name":"Protsyuk"},{"full_name":"Becker, Paul F.","last_name":"Becker","first_name":"Paul F."},{"last_name":"Stefanescu","first_name":"Cristina","full_name":"Stefanescu, Cristina"},{"full_name":"Gorzelanny, Christian","first_name":"Christian","last_name":"Gorzelanny"},{"full_name":"Glaus Garzon, Jesus F.","first_name":"Jesus F.","last_name":"Glaus Garzon"},{"first_name":"Lucia","last_name":"Knopfova","full_name":"Knopfova, Lucia"},{"first_name":"Mathias","last_name":"Heikenwalder","full_name":"Heikenwalder, Mathias"},{"first_name":"Bruno","last_name":"Luckow","full_name":"Luckow, Bruno"},{"last_name":"Schneider","first_name":"Stefan W.","full_name":"Schneider, Stefan W."},{"full_name":"Borsig, Lubor","first_name":"Lubor","last_name":"Borsig"}],"volume":17,"date_updated":"2023-08-25T08:57:01Z","date_created":"2019-03-31T21:59:12Z","publication_identifier":{"issn":["15417786"],"eissn":["15573125"]},"month":"03","oa":1,"external_id":{"isi":["000460099800012"],"pmid":["30552233"]},"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1158/1541-7786.MCR-18-0530"}],"quality_controlled":"1","isi":1,"doi":"10.1158/1541-7786.MCR-18-0530","language":[{"iso":"eng"}],"type":"journal_article","issue":"3","abstract":[{"text":"Increased levels of the chemokine CCL2 in cancer patients are associated with poor prognosis. Experimental evidence suggests that CCL2 correlates with inflammatory monocyte recruitment and induction of vascular activation, but the functionality remains open. Here, we show that endothelial Ccr2 facilitates pulmonary metastasis using an endothelial-specific Ccr2-deficient mouse model (Ccr2ecKO). Similar levels of circulating monocytes and equal leukocyte recruitment to metastatic lesions of Ccr2ecKO and Ccr2fl/fl littermates were observed. The absence of endothelial Ccr2 strongly reduced pulmonary metastasis, while the primary tumor growth was unaffected. Despite a comparable cytokine milieu in Ccr2ecKO and Ccr2fl/fl littermates the absence of vascular permeability induction was observed only in Ccr2ecKO mice. CCL2 stimulation of pulmonary endothelial cells resulted in increased phosphorylation of MLC2, endothelial cell retraction, and vascular leakiness that was blocked by an addition of a CCR2 inhibitor. These data demonstrate that endothelial CCR2 expression is required for tumor cell extravasation and pulmonary metastasis.\r\n\r\nImplications: The findings provide mechanistic insight into how CCL2–CCR2 signaling in endothelial cells promotes their activation through myosin light chain phosphorylation, resulting in endothelial retraction and enhanced tumor cell migration and metastasis.","lang":"eng"}],"_id":"6190","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","intvolume":" 17","status":"public","title":"CCL2 is a vascular permeability factor inducing CCR2-dependent endothelial retraction during lung metastasis","oa_version":"Published Version","scopus_import":"1","article_processing_charge":"No","day":"01","citation":{"ista":"Roblek M, Protsyuk D, Becker PF, Stefanescu C, Gorzelanny C, Glaus Garzon JF, Knopfova L, Heikenwalder M, Luckow B, Schneider SW, Borsig L. 2019. CCL2 is a vascular permeability factor inducing CCR2-dependent endothelial retraction during lung metastasis. Molecular Cancer Research. 17(3), 783–793.","apa":"Roblek, M., Protsyuk, D., Becker, P. F., Stefanescu, C., Gorzelanny, C., Glaus Garzon, J. F., … Borsig, L. (2019). CCL2 is a vascular permeability factor inducing CCR2-dependent endothelial retraction during lung metastasis. Molecular Cancer Research. AACR. https://doi.org/10.1158/1541-7786.MCR-18-0530","ieee":"M. Roblek et al., “CCL2 is a vascular permeability factor inducing CCR2-dependent endothelial retraction during lung metastasis,” Molecular Cancer Research, vol. 17, no. 3. AACR, pp. 783–793, 2019.","ama":"Roblek M, Protsyuk D, Becker PF, et al. CCL2 is a vascular permeability factor inducing CCR2-dependent endothelial retraction during lung metastasis. Molecular Cancer Research. 2019;17(3):783-793. doi:10.1158/1541-7786.MCR-18-0530","chicago":"Roblek, Marko, Darya Protsyuk, Paul F. Becker, Cristina Stefanescu, Christian Gorzelanny, Jesus F. Glaus Garzon, Lucia Knopfova, et al. “CCL2 Is a Vascular Permeability Factor Inducing CCR2-Dependent Endothelial Retraction during Lung Metastasis.” Molecular Cancer Research. AACR, 2019. https://doi.org/10.1158/1541-7786.MCR-18-0530.","mla":"Roblek, Marko, et al. “CCL2 Is a Vascular Permeability Factor Inducing CCR2-Dependent Endothelial Retraction during Lung Metastasis.” Molecular Cancer Research, vol. 17, no. 3, AACR, 2019, pp. 783–93, doi:10.1158/1541-7786.MCR-18-0530.","short":"M. Roblek, D. Protsyuk, P.F. Becker, C. Stefanescu, C. Gorzelanny, J.F. Glaus Garzon, L. Knopfova, M. Heikenwalder, B. Luckow, S.W. Schneider, L. Borsig, Molecular Cancer Research 17 (2019) 783–793."},"publication":"Molecular Cancer Research","page":"783-793","article_type":"original","date_published":"2019-03-01T00:00:00Z"},{"publication_status":"published","publisher":"Springer Nature","department":[{"_id":"DaSi"}],"year":"2019","date_updated":"2023-08-30T07:27:55Z","date_created":"2019-11-25T07:55:01Z","volume":2,"author":[{"full_name":"Nagano, Makoto","last_name":"Nagano","first_name":"Makoto"},{"first_name":"Junko Y.","last_name":"Toshima","full_name":"Toshima, Junko Y."},{"first_name":"Daria E","last_name":"Siekhaus","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8323-8353","full_name":"Siekhaus, Daria E"},{"full_name":"Toshima, Jiro","last_name":"Toshima","first_name":"Jiro"}],"article_number":"419","file_date_updated":"2020-07-14T12:47:49Z","quality_controlled":"1","isi":1,"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000496767800005"]},"language":[{"iso":"eng"}],"doi":"10.1038/s42003-019-0670-5","month":"11","publication_identifier":{"issn":["2399-3642"]},"title":"Rab5-mediated endosome formation is regulated at the trans-Golgi network","status":"public","ddc":["570"],"intvolume":" 2","_id":"7097","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file":[{"checksum":"c63c69a264fc8a0e52f2b0d482f3bdae","date_created":"2019-11-25T07:58:05Z","date_updated":"2020-07-14T12:47:49Z","relation":"main_file","file_id":"7098","content_type":"application/pdf","file_size":2626069,"creator":"dernst","access_level":"open_access","file_name":"2019_CommunicBiology_Nagano.pdf"}],"oa_version":"Published Version","type":"journal_article","abstract":[{"lang":"eng","text":"Early endosomes, also called sorting endosomes, are known to mature into late endosomesvia the Rab5-mediated endolysosomal trafficking pathway. Thus, early endosome existence isthought to be maintained by the continual fusion of transport vesicles from the plasmamembrane and thetrans-Golgi network (TGN). Here we show instead that endocytosis isdispensable and post-Golgi vesicle transport is crucial for the formation of endosomes andthe subsequent endolysosomal traffic regulated by yeast Rab5 Vps21p. Fittingly, all threeproteins required for endosomal nucleotide exchange on Vps21p arefirst recruited to theTGN before transport to the endosome, namely the GEF Vps9p and the epsin-relatedadaptors Ent3/5p. The TGN recruitment of these components is distinctly controlled, withVps9p appearing to require the Arf1p GTPase, and the Rab11s, Ypt31p/32p. These resultsprovide a different view of endosome formation and identify the TGN as a critical location forregulating progress through the endolysosomal trafficking pathway."}],"issue":"1","article_type":"original","publication":"Communications Biology","citation":{"ama":"Nagano M, Toshima JY, Siekhaus DE, Toshima J. Rab5-mediated endosome formation is regulated at the trans-Golgi network. Communications Biology. 2019;2(1). doi:10.1038/s42003-019-0670-5","ista":"Nagano M, Toshima JY, Siekhaus DE, Toshima J. 2019. Rab5-mediated endosome formation is regulated at the trans-Golgi network. Communications Biology. 2(1), 419.","ieee":"M. Nagano, J. Y. Toshima, D. E. Siekhaus, and J. Toshima, “Rab5-mediated endosome formation is regulated at the trans-Golgi network,” Communications Biology, vol. 2, no. 1. Springer Nature, 2019.","apa":"Nagano, M., Toshima, J. Y., Siekhaus, D. E., & Toshima, J. (2019). Rab5-mediated endosome formation is regulated at the trans-Golgi network. Communications Biology. Springer Nature. https://doi.org/10.1038/s42003-019-0670-5","mla":"Nagano, Makoto, et al. “Rab5-Mediated Endosome Formation Is Regulated at the Trans-Golgi Network.” Communications Biology, vol. 2, no. 1, 419, Springer Nature, 2019, doi:10.1038/s42003-019-0670-5.","short":"M. Nagano, J.Y. Toshima, D.E. Siekhaus, J. Toshima, Communications Biology 2 (2019).","chicago":"Nagano, Makoto, Junko Y. Toshima, Daria E Siekhaus, and Jiro Toshima. “Rab5-Mediated Endosome Formation Is Regulated at the Trans-Golgi Network.” Communications Biology. Springer Nature, 2019. https://doi.org/10.1038/s42003-019-0670-5."},"date_published":"2019-11-15T00:00:00Z","scopus_import":"1","day":"15","article_processing_charge":"No","has_accepted_license":"1"},{"language":[{"iso":"eng"}],"doi":"10.1038/s41467-019-13543-1","quality_controlled":"1","isi":1,"project":[{"grant_number":"M02379","_id":"264CBBAC-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Modeling epithelial tissue mechanics during cell invasion"}],"external_id":{"isi":["000500508100001"],"pmid":["31797871"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"month":"12","publication_identifier":{"eissn":["20411723"]},"date_updated":"2023-09-06T14:08:21Z","date_created":"2019-12-15T23:00:43Z","volume":10,"author":[{"first_name":"Katarzyna","last_name":"Retzer","full_name":"Retzer, Katarzyna"},{"full_name":"Akhmanova, Maria","orcid":"0000-0003-1522-3162","id":"3425EC26-F248-11E8-B48F-1D18A9856A87","last_name":"Akhmanova","first_name":"Maria"},{"full_name":"Konstantinova, Nataliia","first_name":"Nataliia","last_name":"Konstantinova"},{"full_name":"Malínská, Kateřina","first_name":"Kateřina","last_name":"Malínská"},{"full_name":"Leitner, Johannes","last_name":"Leitner","first_name":"Johannes"},{"first_name":"Jan","last_name":"Petrášek","full_name":"Petrášek, Jan"},{"last_name":"Luschnig","first_name":"Christian","full_name":"Luschnig, Christian"}],"publication_status":"published","department":[{"_id":"DaSi"}],"publisher":"Springer Nature","year":"2019","pmid":1,"file_date_updated":"2020-07-14T12:47:52Z","article_number":"5516","date_published":"2019-12-01T00:00:00Z","article_type":"original","publication":"Nature Communications","citation":{"ama":"Retzer K, Akhmanova M, Konstantinova N, et al. Brassinosteroid signaling delimits root gravitropism via sorting of the Arabidopsis PIN2 auxin transporter. Nature Communications. 2019;10. doi:10.1038/s41467-019-13543-1","ieee":"K. Retzer et al., “Brassinosteroid signaling delimits root gravitropism via sorting of the Arabidopsis PIN2 auxin transporter,” Nature Communications, vol. 10. Springer Nature, 2019.","apa":"Retzer, K., Akhmanova, M., Konstantinova, N., Malínská, K., Leitner, J., Petrášek, J., & Luschnig, C. (2019). Brassinosteroid signaling delimits root gravitropism via sorting of the Arabidopsis PIN2 auxin transporter. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-019-13543-1","ista":"Retzer K, Akhmanova M, Konstantinova N, Malínská K, Leitner J, Petrášek J, Luschnig C. 2019. Brassinosteroid signaling delimits root gravitropism via sorting of the Arabidopsis PIN2 auxin transporter. Nature Communications. 10, 5516.","short":"K. Retzer, M. Akhmanova, N. Konstantinova, K. Malínská, J. Leitner, J. Petrášek, C. Luschnig, Nature Communications 10 (2019).","mla":"Retzer, Katarzyna, et al. “Brassinosteroid Signaling Delimits Root Gravitropism via Sorting of the Arabidopsis PIN2 Auxin Transporter.” Nature Communications, vol. 10, 5516, Springer Nature, 2019, doi:10.1038/s41467-019-13543-1.","chicago":"Retzer, Katarzyna, Maria Akhmanova, Nataliia Konstantinova, Kateřina Malínská, Johannes Leitner, Jan Petrášek, and Christian Luschnig. “Brassinosteroid Signaling Delimits Root Gravitropism via Sorting of the Arabidopsis PIN2 Auxin Transporter.” Nature Communications. Springer Nature, 2019. https://doi.org/10.1038/s41467-019-13543-1."},"day":"01","article_processing_charge":"No","has_accepted_license":"1","scopus_import":"1","file":[{"relation":"main_file","file_id":"7184","checksum":"77e8720a8e0f3091b98159f85be40893","date_updated":"2020-07-14T12:47:52Z","date_created":"2019-12-16T07:37:50Z","access_level":"open_access","file_name":"2019_NatureComm_Retzer.pdf","content_type":"application/pdf","file_size":5156533,"creator":"dernst"}],"oa_version":"Published Version","status":"public","title":"Brassinosteroid signaling delimits root gravitropism via sorting of the Arabidopsis PIN2 auxin transporter","ddc":["570"],"intvolume":" 10","_id":"7180","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","abstract":[{"text":"Arabidopsis PIN2 protein directs transport of the phytohormone auxin from the root tip into the root elongation zone. Variation in hormone transport, which depends on a delicate interplay between PIN2 sorting to and from polar plasma membrane domains, determines root growth. By employing a constitutively degraded version of PIN2, we identify brassinolides as antagonists of PIN2 endocytosis. This response does not require de novo protein synthesis, but involves early events in canonical brassinolide signaling. Brassinolide-controlled adjustments in PIN2 sorting and intracellular distribution governs formation of a lateral PIN2 gradient in gravistimulated roots, coinciding with adjustments in auxin signaling and directional root growth. Strikingly, simulations indicate that PIN2 gradient formation is no prerequisite for root bending but rather dampens asymmetric auxin flow and signaling. Crosstalk between brassinolide signaling and endocytic PIN2 sorting, thus, appears essential for determining the rate of gravity-induced root curvature via attenuation of differential cell elongation.","lang":"eng"}],"type":"journal_article"},{"doi":"10.1523/JNEUROSCI.1059-18.2018","language":[{"iso":"eng"}],"oa":1,"external_id":{"pmid":["30504274"],"isi":["000455189900006"]},"project":[{"_id":"2536F660-B435-11E9-9278-68D0E5697425","grant_number":"334077","call_identifier":"FP7","name":"Investigating the role of transporters in invasive migration through junctions"}],"quality_controlled":"1","isi":1,"month":"01","author":[{"full_name":"Trébuchet, Guillaume","first_name":"Guillaume","last_name":"Trébuchet"},{"full_name":"Cattenoz, Pierre B","first_name":"Pierre B","last_name":"Cattenoz"},{"first_name":"János","last_name":"Zsámboki","full_name":"Zsámboki, János"},{"full_name":"Mazaud, David","first_name":"David","last_name":"Mazaud"},{"first_name":"Daria E","last_name":"Siekhaus","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8323-8353","full_name":"Siekhaus, Daria E"},{"full_name":"Fanto, Manolis","first_name":"Manolis","last_name":"Fanto"},{"first_name":"Angela","last_name":"Giangrande","full_name":"Giangrande, Angela"}],"volume":39,"date_updated":"2023-09-19T10:10:55Z","date_created":"2018-12-11T11:44:07Z","pmid":1,"year":"2019","acknowledgement":"This work was supported by INSERM, CNRS, UDS, Ligue Régionale contre le Cancer, Hôpital de Strasbourg, Association pour la Recherche sur le Cancer (ARC) and Agence Nationale de la Recherche (ANR) grants. P.B.C. was funded by the ANR and by the ARSEP (Fondation pour l'Aide à la Recherche sur la Sclérose en Plaques), and G.T. by governmental and ARC fellowships. This work was also supported by grants from the Ataxia UK (2491) and the NC3R (NC/L000199/1) awarded to M.F. The Institut de Génétique et de Biologie Moléculaire et Cellulaire was also supported by a French state fund through the ANR labex. D.E.S. was funded by Marie Curie Grant CIG 334077/IRTIM. We thank B. Altenhein, K. Brückner, M. Crozatier, L. Waltzer, M. Logan, E. Kurant, R. Reuter, E. Kurucz, J.L Dimarcq, J. Hoffmann, C. Goodman, the DHSB, and the BDSC for reagents and flies. We also thank all of the laboratory members for comments on the manuscript; C. Diebold, C. Delaporte, M. Pezze, the fly, and imaging and antibody facilities for technical assistance; and D. Dembele for help with statistics. In addition, we thank Alison Brewer for help with Luciferase assays.","publisher":"Society for Neuroscience","department":[{"_id":"DaSi"}],"publication_status":"published","publist_id":"8048","ec_funded":1,"file_date_updated":"2020-10-02T09:33:28Z","date_published":"2019-01-09T00:00:00Z","citation":{"ama":"Trébuchet G, Cattenoz PB, Zsámboki J, et al. The Repo homeodomain transcription factor suppresses hematopoiesis in Drosophila and preserves the glial fate. Journal of Neuroscience. 2019;39(2):238-255. doi:10.1523/JNEUROSCI.1059-18.2018","ieee":"G. Trébuchet et al., “The Repo homeodomain transcription factor suppresses hematopoiesis in Drosophila and preserves the glial fate,” Journal of Neuroscience, vol. 39, no. 2. Society for Neuroscience, pp. 238–255, 2019.","apa":"Trébuchet, G., Cattenoz, P. B., Zsámboki, J., Mazaud, D., Siekhaus, D. E., Fanto, M., & Giangrande, A. (2019). The Repo homeodomain transcription factor suppresses hematopoiesis in Drosophila and preserves the glial fate. Journal of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.1059-18.2018","ista":"Trébuchet G, Cattenoz PB, Zsámboki J, Mazaud D, Siekhaus DE, Fanto M, Giangrande A. 2019. The Repo homeodomain transcription factor suppresses hematopoiesis in Drosophila and preserves the glial fate. Journal of Neuroscience. 39(2), 238–255.","short":"G. Trébuchet, P.B. Cattenoz, J. Zsámboki, D. Mazaud, D.E. Siekhaus, M. Fanto, A. Giangrande, Journal of Neuroscience 39 (2019) 238–255.","mla":"Trébuchet, Guillaume, et al. “The Repo Homeodomain Transcription Factor Suppresses Hematopoiesis in Drosophila and Preserves the Glial Fate.” Journal of Neuroscience, vol. 39, no. 2, Society for Neuroscience, 2019, pp. 238–55, doi:10.1523/JNEUROSCI.1059-18.2018.","chicago":"Trébuchet, Guillaume, Pierre B Cattenoz, János Zsámboki, David Mazaud, Daria E Siekhaus, Manolis Fanto, and Angela Giangrande. “The Repo Homeodomain Transcription Factor Suppresses Hematopoiesis in Drosophila and Preserves the Glial Fate.” Journal of Neuroscience. Society for Neuroscience, 2019. https://doi.org/10.1523/JNEUROSCI.1059-18.2018."},"publication":"Journal of Neuroscience","page":"238-255","article_type":"original","has_accepted_license":"1","article_processing_charge":"No","day":"09","scopus_import":"1","oa_version":"Published Version","file":[{"success":1,"checksum":"8f6925eb4cd1e8747d8ea25929c68de6","date_updated":"2020-10-02T09:33:28Z","date_created":"2020-10-02T09:33:28Z","file_id":"8596","relation":"main_file","creator":"dernst","file_size":9455414,"content_type":"application/pdf","access_level":"open_access","file_name":"2019_JournNeuroscience_Trebuchet.pdf"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"8","intvolume":" 39","status":"public","ddc":["570"],"title":"The Repo homeodomain transcription factor suppresses hematopoiesis in Drosophila and preserves the glial fate","issue":"2","abstract":[{"lang":"eng","text":"Despite their different origins, Drosophila glia and hemocytes are related cell populations that provide an immune function. Drosophila hemocytes patrol the body cavity and act as macrophages outside the nervous system whereas glia originate from the neuroepithelium and provide the scavenger population of the nervous system. Drosophila glia are hence the functional orthologs of vertebrate microglia, even though the latter are cells of immune origin that subsequently move into the brain during development. Interestingly, the Drosophila immune cells within (glia) and outside the nervous system (hemocytes) require the same transcription factor Glide/Gcm for their development. This raises the issue of how do glia specifically differentiate in the nervous system and hemocytes in the procephalic mesoderm. The Repo homeodomain transcription factor and pan-glial direct target of Glide/Gcm is known to ensure glial terminal differentiation. Here we show that Repo also takes center stage in the process that discriminates between glia and hemocytes. First, Repo expression is repressed in the hemocyte anlagen by mesoderm-specific factors. Second, Repo ectopic activation in the procephalic mesoderm is sufficient to repress the expression of hemocyte-specific genes. Third, the lack of Repo triggers the expression of hemocyte markers in glia. Thus, a complex network of tissue-specific cues biases the potential of Glide/Gcm. These data allow us to revise the concept of fate determinants and help us understand the bases of cell specification. Both sexes were analyzed.SIGNIFICANCE STATEMENTDistinct cell types often require the same pioneer transcription factor, raising the issue of how does one factor trigger different fates. In Drosophila, glia and hemocytes provide a scavenger activity within and outside the nervous system, respectively. While they both require the Glide/Gcm transcription factor, glia originate from the ectoderm, hemocytes from the mesoderm. Here we show that tissue-specific factors inhibit the gliogenic potential of Glide/Gcm in the mesoderm by repressing the expression of the homeodomain protein Repo, a major glial-specific target of Glide/Gcm. Repo expression in turn inhibits the expression of hemocyte-specific genes in the nervous system. These cell-specific networks secure the establishment of the glial fate only in the nervous system and allow cell diversification."}],"type":"journal_article"},{"type":"journal_article","abstract":[{"lang":"eng","text":"Aberrant display of the truncated core1 O-glycan T-antigen is a common feature of human cancer cells that correlates with metastasis. Here we show that T-antigen in Drosophila melanogaster macrophages is involved in their developmentally programmed tissue invasion. Higher macrophage T-antigen levels require an atypical major facilitator superfamily (MFS) member that we named Minerva which enables macrophage dissemination and invasion. We characterize for the first time the T and Tn glycoform O-glycoproteome of the Drosophila melanogaster embryo, and determine that Minerva increases the presence of T-antigen on proteins in pathways previously linked to cancer, most strongly on the sulfhydryl oxidase Qsox1 which we show is required for macrophage tissue entry. Minerva’s vertebrate ortholog, MFSD1, rescues the minerva mutant’s migration and T-antigen glycosylation defects. We thus identify a key conserved regulator that orchestrates O-glycosylation on a protein subset to activate a program governing migration steps important for both development and cancer metastasis."}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"6187","intvolume":" 8","title":"A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion","status":"public","ddc":["570"],"file":[{"relation":"main_file","file_id":"6188","date_created":"2019-03-28T14:00:41Z","date_updated":"2020-07-14T12:47:23Z","checksum":"cc0d1a512559d52e7e7cb0e9b9854b40","file_name":"2019_eLife_Valoskova.pdf","access_level":"open_access","file_size":4496017,"content_type":"application/pdf","creator":"dernst"}],"oa_version":"Published Version","scopus_import":"1","article_processing_charge":"No","has_accepted_license":"1","day":"26","citation":{"chicago":"Valosková, Katarina, Julia Bicher, Marko Roblek, Shamsi Emtenani, Attila György, Michaela Misova, Aparna Ratheesh, et al. “A Conserved Major Facilitator Superfamily Member Orchestrates a Subset of O-Glycosylation to Aid Macrophage Tissue Invasion.” ELife. eLife Sciences Publications, 2019. https://doi.org/10.7554/elife.41801.","mla":"Valosková, Katarina, et al. “A Conserved Major Facilitator Superfamily Member Orchestrates a Subset of O-Glycosylation to Aid Macrophage Tissue Invasion.” ELife, vol. 8, e41801, eLife Sciences Publications, 2019, doi:10.7554/elife.41801.","short":"K. Valosková, J. Bicher, M. Roblek, S. Emtenani, A. György, M. Misova, A. Ratheesh, P. Rodrigues, K. Shkarina, I.S.B. Larsen, S.Y. Vakhrushev, H. Clausen, D.E. Siekhaus, ELife 8 (2019).","ista":"Valosková K, Bicher J, Roblek M, Emtenani S, György A, Misova M, Ratheesh A, Rodrigues P, Shkarina K, Larsen ISB, Vakhrushev SY, Clausen H, Siekhaus DE. 2019. A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion. eLife. 8, e41801.","apa":"Valosková, K., Bicher, J., Roblek, M., Emtenani, S., György, A., Misova, M., … Siekhaus, D. E. (2019). A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.41801","ieee":"K. Valosková et al., “A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion,” eLife, vol. 8. eLife Sciences Publications, 2019.","ama":"Valosková K, Bicher J, Roblek M, et al. A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion. eLife. 2019;8. doi:10.7554/elife.41801"},"publication":"eLife","date_published":"2019-03-26T00:00:00Z","article_number":"e41801","ec_funded":1,"file_date_updated":"2020-07-14T12:47:23Z","year":"2019","department":[{"_id":"DaSi"}],"publisher":"eLife Sciences Publications","publication_status":"published","related_material":{"link":[{"description":"News on IST Homepage","relation":"press_release","url":"https://ist.ac.at/en/news/new-gene-potentially-involved-in-metastasis-identified/"}],"record":[{"id":"6530","relation":"dissertation_contains"},{"id":"8983","status":"public","relation":"dissertation_contains"},{"id":"6546","relation":"dissertation_contains","status":"public"}]},"author":[{"last_name":"Valosková","first_name":"Katarina","id":"46F146FC-F248-11E8-B48F-1D18A9856A87","full_name":"Valosková, Katarina"},{"last_name":"Biebl","first_name":"Julia","id":"3CCBB46E-F248-11E8-B48F-1D18A9856A87","full_name":"Biebl, Julia"},{"full_name":"Roblek, Marko","last_name":"Roblek","first_name":"Marko","orcid":"0000-0001-9588-1389","id":"3047D808-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Emtenani","first_name":"Shamsi","orcid":"0000-0001-6981-6938","id":"49D32318-F248-11E8-B48F-1D18A9856A87","full_name":"Emtenani, Shamsi"},{"full_name":"György, Attila","orcid":"0000-0002-1819-198X","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","last_name":"György","first_name":"Attila"},{"full_name":"Misova, Michaela","id":"495A3C32-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2427-6856","first_name":"Michaela","last_name":"Misova"},{"full_name":"Ratheesh, Aparna","id":"2F064CFE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7190-0776","first_name":"Aparna","last_name":"Ratheesh"},{"full_name":"Rodrigues, Patricia","last_name":"Rodrigues","first_name":"Patricia","id":"2CE4065A-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Katerina","last_name":"Shkarina","full_name":"Shkarina, Katerina"},{"full_name":"Larsen, Ida Signe Bohse","last_name":"Larsen","first_name":"Ida Signe Bohse"},{"first_name":"Sergey Y","last_name":"Vakhrushev","full_name":"Vakhrushev, Sergey Y"},{"full_name":"Clausen, Henrik","first_name":"Henrik","last_name":"Clausen"},{"full_name":"Siekhaus, Daria E","orcid":"0000-0001-8323-8353","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","last_name":"Siekhaus","first_name":"Daria E"}],"volume":8,"date_created":"2019-03-28T13:37:45Z","date_updated":"2024-03-28T23:30:30Z","publication_identifier":{"issn":["2050-084X"]},"month":"03","oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000462530200001"]},"project":[{"_id":"253CDE40-B435-11E9-9278-68D0E5697425","grant_number":"24283","name":"Examination of the role of a MFS transporter in the migration of Drosophila immune cells"},{"_id":"253B6E48-B435-11E9-9278-68D0E5697425","grant_number":"P29638","call_identifier":"FWF","name":"The role of Drosophila TNF alpha in immune cell invasion"},{"call_identifier":"FP7","name":"Investigating the role of transporters in invasive migration through junctions","grant_number":"334077","_id":"2536F660-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FP7","name":"Breaking barriers: Investigating the junctional and mechanobiological changes underlying the ability of Drosophila immune cells to invade an epithelium","_id":"25388084-B435-11E9-9278-68D0E5697425","grant_number":"329540"},{"call_identifier":"H2020","name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385"}],"quality_controlled":"1","isi":1,"doi":"10.7554/elife.41801","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"LifeSc"}]},{"has_accepted_license":"1","article_processing_charge":"No","day":"07","page":"141","citation":{"ista":"Valosková K. 2019. The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration. Institute of Science and Technology Austria.","apa":"Valosková, K. (2019). The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6546","ieee":"K. Valosková, “The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration,” Institute of Science and Technology Austria, 2019.","ama":"Valosková K. The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration. 2019. doi:10.15479/AT:ISTA:6546","chicago":"Valosková, Katarina. “The Role of a Highly Conserved Major Facilitator Superfamily Member in Drosophila Embryonic Macrophage Migration.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6546.","mla":"Valosková, Katarina. The Role of a Highly Conserved Major Facilitator Superfamily Member in Drosophila Embryonic Macrophage Migration. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6546.","short":"K. Valosková, The Role of a Highly Conserved Major Facilitator Superfamily Member in Drosophila Embryonic Macrophage Migration, Institute of Science and Technology Austria, 2019."},"date_published":"2019-06-07T00:00:00Z","alternative_title":["ISTA Thesis"],"type":"dissertation","abstract":[{"text":"Invasive migration plays a crucial role not only during development and homeostasis but also in pathological states, such as tumor metastasis. Drosophila macrophage migration into the extended germband is an interesting system to study invasive migration. It carries similarities to immune cell transmigration and cancer cell invasion, therefore studying this process could also bring new understanding of invasion in higher organisms. In our work, we uncover a highly conserved member of the major facilitator family that plays a role in tissue invasion through regulation of glycosylation on a subgroup of proteins and/or by aiding the precise timing of DN-Cadherin downregulation. \r\n\r\nAberrant display of the truncated core1 O-glycan T-antigen is a common feature of human cancer cells that correlates with metastasis. Here we show that T-antigen in Drosophila melanogaster macrophages is involved in their developmentally programmed tissue invasion. Higher macrophage T-antigen levels require an atypical major facilitator superfamily (MFS) member that we named Minerva which enables macrophage dissemination and invasion. We characterize for the first time the T and Tn glycoform O-glycoproteome of the Drosophila melanogaster embryo, and determine that Minerva increases the presence of T-antigen on proteins in pathways previously linked to cancer, most strongly on the sulfhydryl oxidase Qsox1 which we show is required for macrophage tissue entry. Minerva’s vertebrate ortholog, MFSD1, rescues the minerva mutant’s migration and T-antigen glycosylation defects. We thus identify \r\na key conserved regulator that orchestrates O-glycosylation on a protein subset to activate \r\na program governing migration steps important for both development and cancer metastasis. \r\n","lang":"eng"}],"status":"public","ddc":["570"],"title":"The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"6546","file":[{"access_level":"closed","file_name":"Katarina Valoskova_PhD thesis_final version.docx","embargo_to":"open_access","creator":"khribikova","file_size":14110626,"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_id":"6549","relation":"source_file","checksum":"68949c2d96210b45b981a23e9c9cd93c","date_created":"2019-06-07T13:00:04Z","date_updated":"2020-07-14T12:47:33Z"},{"access_level":"open_access","file_name":"Katarina Valoskova_PhD thesis_final version.pdf","file_size":10054156,"content_type":"application/pdf","creator":"khribikova","relation":"main_file","embargo":"2020-06-07","file_id":"6550","checksum":"555329cd76e196c96f5278c480ee2e6e","date_created":"2019-06-07T13:00:08Z","date_updated":"2021-02-11T11:17:14Z"}],"oa_version":"Published Version","publication_identifier":{"issn":["2663-337X"]},"month":"06","project":[{"grant_number":"24283","_id":"253CDE40-B435-11E9-9278-68D0E5697425","name":"Examination of the role of a MFS transporter in the migration of Drosophila immune cells"}],"oa":1,"language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"Bio"}],"supervisor":[{"first_name":"Daria E","last_name":"Siekhaus","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8323-8353","full_name":"Siekhaus, Daria E"}],"degree_awarded":"PhD","doi":"10.15479/AT:ISTA:6546","file_date_updated":"2021-02-11T11:17:14Z","publisher":"Institute of Science and Technology Austria","department":[{"_id":"DaSi"}],"publication_status":"published","year":"2019","date_created":"2019-06-07T12:49:19Z","date_updated":"2023-09-19T10:15:54Z","related_material":{"record":[{"status":"public","relation":"part_of_dissertation","id":"6187"},{"status":"public","relation":"part_of_dissertation","id":"544"}]},"author":[{"id":"46F146FC-F248-11E8-B48F-1D18A9856A87","last_name":"Valosková","first_name":"Katarina","full_name":"Valosková, Katarina"}]}]