--- _id: '10536' 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. 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. article_number: '765151' article_processing_charge: No article_type: original author: - first_name: Cristina full_name: Stefanescu, Cristina last_name: Stefanescu - first_name: Merel full_name: Van Gogh, Merel last_name: Van Gogh - first_name: Marko full_name: Roblek, Marko id: 3047D808-F248-11E8-B48F-1D18A9856A87 last_name: Roblek orcid: 0000-0001-9588-1389 - first_name: Mathias full_name: Heikenwalder, Mathias last_name: Heikenwalder - first_name: Lubor full_name: Borsig, Lubor last_name: Borsig citation: 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 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 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. 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. 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. 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). date_created: 2021-12-12T23:01:27Z date_published: 2021-11-18T00:00:00Z date_updated: 2023-08-17T06:20:32Z day: '18' ddc: - '610' department: - _id: DaSi doi: 10.3389/fonc.2021.765151 external_id: isi: - '000726603400001' pmid: - '34868988' file: - access_level: open_access checksum: 56cbac80e6891ce750511a30161b7792 content_type: application/pdf creator: alisjak date_created: 2021-12-13T13:32:37Z date_updated: 2021-12-13T13:32:37Z file_id: '10539' file_name: 2021_Frontiers_Stefanescu.pdf file_size: 9245199 relation: main_file success: 1 file_date_updated: 2021-12-13T13:32:37Z has_accepted_license: '1' intvolume: ' 11' isi: 1 language: - iso: eng license: https://creativecommons.org/licenses/by/4.0/ month: '11' oa: 1 oa_version: Published Version pmid: 1 publication: Frontiers in Oncology publication_identifier: eissn: - 2234-943X publication_status: published publisher: Frontiers quality_controlled: '1' scopus_import: '1' status: public title: TGFβ signaling in myeloid cells promotes lung and liver metastasis through different mechanisms tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 11 year: '2021' ... --- _id: '7466' abstract: - lang: eng 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. article_number: e51595 article_processing_charge: No article_type: original author: - first_name: Katrin full_name: Kierdorf, Katrin last_name: Kierdorf - first_name: Fabian full_name: Hersperger, Fabian last_name: Hersperger - first_name: Jessica full_name: Sharrock, Jessica last_name: Sharrock - first_name: Crystal M. full_name: Vincent, Crystal M. last_name: Vincent - first_name: Pinar full_name: Ustaoglu, Pinar last_name: Ustaoglu - first_name: Jiawen full_name: Dou, Jiawen last_name: Dou - first_name: Attila full_name: György, Attila id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87 last_name: György orcid: 0000-0002-1819-198X - first_name: Olaf full_name: Groß, Olaf last_name: Groß - first_name: Daria E full_name: Siekhaus, Daria E id: 3D224B9E-F248-11E8-B48F-1D18A9856A87 last_name: Siekhaus orcid: 0000-0001-8323-8353 - first_name: Marc S. full_name: Dionne, Marc S. last_name: Dionne 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 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 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. ieee: K. Kierdorf et al., “Muscle function and homeostasis require cytokine inhibition of AKT activity in Drosophila,” eLife, vol. 9. eLife Sciences Publications, 2020. 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. 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). date_created: 2020-02-09T23:00:51Z date_published: 2020-01-20T00:00:00Z date_updated: 2023-08-17T14:36:39Z day: '20' ddc: - '570' department: - _id: DaSi doi: 10.7554/eLife.51595 external_id: isi: - '000512304800001' file: - access_level: open_access checksum: 3a072be843f416c7a7d532a51dc0addb content_type: application/pdf creator: dernst date_created: 2020-02-10T08:53:16Z date_updated: 2020-07-14T12:47:59Z file_id: '7470' file_name: 2020_eLife_Kierdorf.pdf file_size: 4959933 relation: main_file file_date_updated: 2020-07-14T12:47:59Z has_accepted_license: '1' intvolume: ' 9' isi: 1 language: - iso: eng month: '01' oa: 1 oa_version: Published Version project: - _id: 253B6E48-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P29638 name: Drosophila TNFa´s Funktion in Immunzellen publication: eLife publication_identifier: eissn: - 2050084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' scopus_import: '1' status: public title: Muscle function and homeostasis require cytokine inhibition of AKT activity in Drosophila tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 9 year: '2020' ... --- _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. acknowledged_ssus: - _id: Bio - _id: LifeSc - _id: E-Lib - _id: CampIT acknowledgement: Also, I would like to express my appreciation and thanks to the Bioimaging facility, LSF, GSO, library, and IT people at IST Austria. alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Shamsi full_name: Emtenani, Shamsi id: 49D32318-F248-11E8-B48F-1D18A9856A87 last_name: Emtenani orcid: 0000-0001-6981-6938 citation: ama: Emtenani S. Metabolic regulation of Drosophila macrophage tissue invasion. 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 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. 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. mla: Emtenani, Shamsi. Metabolic Regulation of Drosophila Macrophage Tissue Invasion. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8983. short: S. Emtenani, Metabolic Regulation of Drosophila Macrophage Tissue Invasion, Institute of Science and Technology Austria, 2020. date_created: 2020-12-30T15:41:26Z date_published: 2020-12-30T00:00:00Z date_updated: 2023-09-07T13:24:17Z day: '30' ddc: - '570' degree_awarded: PhD department: - _id: DaSi doi: 10.15479/AT:ISTA:8983 file: - access_level: open_access checksum: ec2797ab7a6f253b35df0572b36d1b43 content_type: application/pdf creator: semtenan date_created: 2020-12-30T15:34:01Z date_updated: 2021-12-31T23:30:04Z embargo: 2021-12-30 file_id: '8984' file_name: Thesis_Shamsi_Emtenani_pdfA.pdf file_size: 10848175 relation: main_file - access_level: closed checksum: cc30e6608a9815414024cf548dff3b3a content_type: application/pdf creator: semtenan date_created: 2020-12-30T15:37:36Z date_updated: 2021-12-31T23:30:04Z embargo_to: open_access file_id: '8985' file_name: Thesis_Shamsi_Emtenani_source file.pdf file_size: 10073648 relation: source_file file_date_updated: 2021-12-31T23:30:04Z has_accepted_license: '1' language: - iso: eng month: '12' oa: 1 oa_version: Published Version page: '141' publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '8557' relation: part_of_dissertation status: public - id: '6187' relation: part_of_dissertation status: public status: public supervisor: - first_name: Daria E full_name: Siekhaus, Daria E id: 3D224B9E-F248-11E8-B48F-1D18A9856A87 last_name: Siekhaus orcid: 0000-0001-8323-8353 title: Metabolic regulation of Drosophila macrophage tissue invasion type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2020' ... --- _id: '8557' 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. acknowledged_ssus: - _id: LifeSc 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.' article_processing_charge: No author: - first_name: Vera full_name: Belyaeva, Vera id: 47F080FE-F248-11E8-B48F-1D18A9856A87 last_name: Belyaeva - first_name: Stephanie full_name: Wachner, Stephanie id: 2A95E7B0-F248-11E8-B48F-1D18A9856A87 last_name: Wachner - first_name: Igor full_name: Gridchyn, Igor id: 4B60654C-F248-11E8-B48F-1D18A9856A87 last_name: Gridchyn orcid: 0000-0002-1807-1929 - first_name: Markus full_name: Linder, Markus last_name: Linder - first_name: Shamsi full_name: Emtenani, Shamsi id: 49D32318-F248-11E8-B48F-1D18A9856A87 last_name: Emtenani orcid: 0000-0001-6981-6938 - first_name: Attila full_name: György, Attila id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87 last_name: György orcid: 0000-0002-1819-198X - first_name: Maria full_name: Sibilia, Maria last_name: Sibilia - first_name: Daria E full_name: Siekhaus, Daria E id: 3D224B9E-F248-11E8-B48F-1D18A9856A87 last_name: Siekhaus orcid: 0000-0001-8323-8353 citation: 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 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 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. ieee: V. Belyaeva et al., “Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance,” bioRxiv. . 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. 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.). date_created: 2020-09-23T09:36:47Z date_published: 2020-09-18T00:00:00Z date_updated: 2024-03-27T23:30:24Z day: '18' department: - _id: DaSi - _id: JoCs doi: 10.1101/2020.09.18.301481 ec_funded: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/2020.09.18.301481 month: '09' oa: 1 oa_version: Preprint project: - _id: 253B6E48-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: P29638 name: Drosophila TNFa´s Funktion in Immunzellen - _id: 2536F660-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '334077' name: Investigating the role of transporters in invasive migration through junctions - _id: 26199CA4-B435-11E9-9278-68D0E5697425 grant_number: '24800' name: Tissue barrier penetration is crucial for immunity and metastasis publication: bioRxiv publication_status: submitted related_material: record: - id: '10614' relation: later_version status: public - id: '8983' relation: dissertation_contains status: public status: public title: Cortical actin properties controlled by Drosophila Fos aid macrophage infiltration against surrounding tissue resistance type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ... --- _id: '6190' abstract: - lang: eng 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." article_processing_charge: No article_type: original author: - first_name: Marko full_name: Roblek, Marko id: 3047D808-F248-11E8-B48F-1D18A9856A87 last_name: Roblek orcid: 0000-0001-9588-1389 - first_name: Darya full_name: Protsyuk, Darya last_name: Protsyuk - first_name: Paul F. full_name: Becker, Paul F. last_name: Becker - first_name: Cristina full_name: Stefanescu, Cristina last_name: Stefanescu - first_name: Christian full_name: Gorzelanny, Christian last_name: Gorzelanny - first_name: Jesus F. full_name: Glaus Garzon, Jesus F. last_name: Glaus Garzon - first_name: Lucia full_name: Knopfova, Lucia last_name: Knopfova - first_name: Mathias full_name: Heikenwalder, Mathias last_name: Heikenwalder - first_name: Bruno full_name: Luckow, Bruno last_name: Luckow - first_name: Stefan W. full_name: Schneider, Stefan W. last_name: Schneider - first_name: Lubor full_name: Borsig, Lubor last_name: Borsig citation: 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 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 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. 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. 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. 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. date_created: 2019-03-31T21:59:12Z date_published: 2019-03-01T00:00:00Z date_updated: 2023-08-25T08:57:01Z day: '01' department: - _id: DaSi doi: 10.1158/1541-7786.MCR-18-0530 external_id: isi: - '000460099800012' pmid: - '30552233' intvolume: ' 17' isi: 1 issue: '3' language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1158/1541-7786.MCR-18-0530 month: '03' oa: 1 oa_version: Published Version page: 783-793 pmid: 1 publication: Molecular Cancer Research publication_identifier: eissn: - '15573125' issn: - '15417786' publication_status: published publisher: AACR quality_controlled: '1' scopus_import: '1' status: public title: CCL2 is a vascular permeability factor inducing CCR2-dependent endothelial retraction during lung metastasis type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 17 year: '2019' ... --- _id: '7097' 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. article_number: '419' article_processing_charge: No article_type: original author: - first_name: Makoto full_name: Nagano, Makoto last_name: Nagano - first_name: Junko Y. full_name: Toshima, Junko Y. last_name: Toshima - first_name: Daria E full_name: Siekhaus, Daria E id: 3D224B9E-F248-11E8-B48F-1D18A9856A87 last_name: Siekhaus orcid: 0000-0001-8323-8353 - first_name: Jiro full_name: Toshima, Jiro last_name: Toshima 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 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 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. 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. 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. 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). date_created: 2019-11-25T07:55:01Z date_published: 2019-11-15T00:00:00Z date_updated: 2023-08-30T07:27:55Z day: '15' ddc: - '570' department: - _id: DaSi doi: 10.1038/s42003-019-0670-5 external_id: isi: - '000496767800005' file: - access_level: open_access checksum: c63c69a264fc8a0e52f2b0d482f3bdae content_type: application/pdf creator: dernst date_created: 2019-11-25T07:58:05Z date_updated: 2020-07-14T12:47:49Z file_id: '7098' file_name: 2019_CommunicBiology_Nagano.pdf file_size: 2626069 relation: main_file file_date_updated: 2020-07-14T12:47:49Z has_accepted_license: '1' intvolume: ' 2' isi: 1 issue: '1' language: - iso: eng month: '11' oa: 1 oa_version: Published Version publication: Communications Biology publication_identifier: issn: - 2399-3642 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Rab5-mediated endosome formation is regulated at the trans-Golgi network tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 2 year: '2019' ... --- _id: '7180' abstract: - lang: eng 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. article_number: '5516' article_processing_charge: No article_type: original author: - first_name: Katarzyna full_name: Retzer, Katarzyna last_name: Retzer - first_name: Maria full_name: Akhmanova, Maria id: 3425EC26-F248-11E8-B48F-1D18A9856A87 last_name: Akhmanova orcid: 0000-0003-1522-3162 - first_name: Nataliia full_name: Konstantinova, Nataliia last_name: Konstantinova - first_name: Kateřina full_name: Malínská, Kateřina last_name: Malínská - first_name: Johannes full_name: Leitner, Johannes last_name: Leitner - first_name: Jan full_name: Petrášek, Jan last_name: Petrášek - first_name: Christian full_name: Luschnig, Christian last_name: Luschnig 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 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 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. 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. 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. 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. short: K. Retzer, M. Akhmanova, N. Konstantinova, K. Malínská, J. Leitner, J. Petrášek, C. Luschnig, Nature Communications 10 (2019). date_created: 2019-12-15T23:00:43Z date_published: 2019-12-01T00:00:00Z date_updated: 2023-09-06T14:08:21Z day: '01' ddc: - '570' department: - _id: DaSi doi: 10.1038/s41467-019-13543-1 external_id: isi: - '000500508100001' pmid: - '31797871' file: - access_level: open_access checksum: 77e8720a8e0f3091b98159f85be40893 content_type: application/pdf creator: dernst date_created: 2019-12-16T07:37:50Z date_updated: 2020-07-14T12:47:52Z file_id: '7184' file_name: 2019_NatureComm_Retzer.pdf file_size: 5156533 relation: main_file file_date_updated: 2020-07-14T12:47:52Z has_accepted_license: '1' intvolume: ' 10' isi: 1 language: - iso: eng month: '12' oa: 1 oa_version: Published Version pmid: 1 project: - _id: 264CBBAC-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: M02379 name: Modeling epithelial tissue mechanics during cell invasion publication: Nature Communications publication_identifier: eissn: - '20411723' publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Brassinosteroid signaling delimits root gravitropism via sorting of the Arabidopsis PIN2 auxin transporter tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 10 year: '2019' ... --- _id: '8' 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. 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. article_processing_charge: No article_type: original author: - first_name: Guillaume full_name: Trébuchet, Guillaume last_name: Trébuchet - first_name: Pierre B full_name: Cattenoz, Pierre B last_name: Cattenoz - first_name: János full_name: Zsámboki, János last_name: Zsámboki - first_name: David full_name: Mazaud, David last_name: Mazaud - first_name: Daria E full_name: Siekhaus, Daria E id: 3D224B9E-F248-11E8-B48F-1D18A9856A87 last_name: Siekhaus orcid: 0000-0001-8323-8353 - first_name: Manolis full_name: Fanto, Manolis last_name: Fanto - first_name: Angela full_name: Giangrande, Angela last_name: Giangrande 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 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 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. 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. 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. 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. short: G. Trébuchet, P.B. Cattenoz, J. Zsámboki, D. Mazaud, D.E. Siekhaus, M. Fanto, A. Giangrande, Journal of Neuroscience 39 (2019) 238–255. date_created: 2018-12-11T11:44:07Z date_published: 2019-01-09T00:00:00Z date_updated: 2023-09-19T10:10:55Z day: '09' ddc: - '570' department: - _id: DaSi doi: 10.1523/JNEUROSCI.1059-18.2018 ec_funded: 1 external_id: isi: - '000455189900006' pmid: - '30504274' file: - access_level: open_access checksum: 8f6925eb4cd1e8747d8ea25929c68de6 content_type: application/pdf creator: dernst date_created: 2020-10-02T09:33:28Z date_updated: 2020-10-02T09:33:28Z file_id: '8596' file_name: 2019_JournNeuroscience_Trebuchet.pdf file_size: 9455414 relation: main_file success: 1 file_date_updated: 2020-10-02T09:33:28Z has_accepted_license: '1' intvolume: ' 39' isi: 1 issue: '2' language: - iso: eng month: '01' oa: 1 oa_version: Published Version page: 238-255 pmid: 1 project: - _id: 2536F660-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '334077' name: Investigating the role of transporters in invasive migration through junctions publication: Journal of Neuroscience publication_status: published publisher: Society for Neuroscience publist_id: '8048' quality_controlled: '1' scopus_import: '1' status: public title: The Repo homeodomain transcription factor suppresses hematopoiesis in Drosophila and preserves the glial fate type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 39 year: '2019' ... --- _id: '6187' 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. acknowledged_ssus: - _id: LifeSc article_number: e41801 article_processing_charge: No author: - first_name: Katarina full_name: Valosková, Katarina id: 46F146FC-F248-11E8-B48F-1D18A9856A87 last_name: Valosková - first_name: Julia full_name: Biebl, Julia id: 3CCBB46E-F248-11E8-B48F-1D18A9856A87 last_name: Biebl - first_name: Marko full_name: Roblek, Marko id: 3047D808-F248-11E8-B48F-1D18A9856A87 last_name: Roblek orcid: 0000-0001-9588-1389 - first_name: Shamsi full_name: Emtenani, Shamsi id: 49D32318-F248-11E8-B48F-1D18A9856A87 last_name: Emtenani orcid: 0000-0001-6981-6938 - first_name: Attila full_name: György, Attila id: 3BCEDBE0-F248-11E8-B48F-1D18A9856A87 last_name: György orcid: 0000-0002-1819-198X - first_name: Michaela full_name: Misova, Michaela id: 495A3C32-F248-11E8-B48F-1D18A9856A87 last_name: Misova orcid: 0000-0003-2427-6856 - first_name: Aparna full_name: Ratheesh, Aparna id: 2F064CFE-F248-11E8-B48F-1D18A9856A87 last_name: Ratheesh orcid: 0000-0001-7190-0776 - first_name: Patricia full_name: Rodrigues, Patricia id: 2CE4065A-F248-11E8-B48F-1D18A9856A87 last_name: Rodrigues - first_name: Katerina full_name: Shkarina, Katerina last_name: Shkarina - first_name: Ida Signe Bohse full_name: Larsen, Ida Signe Bohse last_name: Larsen - first_name: Sergey Y full_name: Vakhrushev, Sergey Y last_name: Vakhrushev - first_name: Henrik full_name: Clausen, Henrik last_name: Clausen - first_name: Daria E full_name: Siekhaus, Daria E id: 3D224B9E-F248-11E8-B48F-1D18A9856A87 last_name: Siekhaus orcid: 0000-0001-8323-8353 citation: 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 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 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. 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. 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. 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). date_created: 2019-03-28T13:37:45Z date_published: 2019-03-26T00:00:00Z date_updated: 2024-03-27T23:30:29Z day: '26' ddc: - '570' department: - _id: DaSi doi: 10.7554/elife.41801 ec_funded: 1 external_id: isi: - '000462530200001' file: - access_level: open_access checksum: cc0d1a512559d52e7e7cb0e9b9854b40 content_type: application/pdf creator: dernst date_created: 2019-03-28T14:00:41Z date_updated: 2020-07-14T12:47:23Z file_id: '6188' file_name: 2019_eLife_Valoskova.pdf file_size: 4496017 relation: main_file file_date_updated: 2020-07-14T12:47:23Z has_accepted_license: '1' intvolume: ' 8' isi: 1 language: - iso: eng month: '03' oa: 1 oa_version: Published Version 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 call_identifier: FWF grant_number: P29638 name: The role of Drosophila TNF alpha in immune cell invasion - _id: 2536F660-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '334077' name: Investigating the role of transporters in invasive migration through junctions - _id: 25388084-B435-11E9-9278-68D0E5697425 call_identifier: FP7 grant_number: '329540' name: 'Breaking barriers: Investigating the junctional and mechanobiological changes underlying the ability of Drosophila immune cells to invade an epithelium' - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program publication: eLife publication_identifier: issn: - 2050-084X publication_status: published publisher: eLife Sciences Publications quality_controlled: '1' 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' relation: dissertation_contains status: public - id: '6546' relation: dissertation_contains status: public scopus_import: '1' status: public title: A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 8 year: '2019' ... --- _id: '6546' abstract: - lang: eng 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" acknowledged_ssus: - _id: Bio alternative_title: - ISTA Thesis article_processing_charge: No author: - first_name: Katarina full_name: Valosková, Katarina id: 46F146FC-F248-11E8-B48F-1D18A9856A87 last_name: Valosková citation: 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 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 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. 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. 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. 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_created: 2019-06-07T12:49:19Z date_published: 2019-06-07T00:00:00Z date_updated: 2023-09-19T10:15:54Z day: '07' ddc: - '570' degree_awarded: PhD department: - _id: DaSi doi: 10.15479/AT:ISTA:6546 file: - access_level: closed checksum: 68949c2d96210b45b981a23e9c9cd93c content_type: application/vnd.openxmlformats-officedocument.wordprocessingml.document creator: khribikova date_created: 2019-06-07T13:00:04Z date_updated: 2020-07-14T12:47:33Z embargo_to: open_access file_id: '6549' file_name: Katarina Valoskova_PhD thesis_final version.docx file_size: 14110626 relation: source_file - access_level: open_access checksum: 555329cd76e196c96f5278c480ee2e6e content_type: application/pdf creator: khribikova date_created: 2019-06-07T13:00:08Z date_updated: 2021-02-11T11:17:14Z embargo: 2020-06-07 file_id: '6550' file_name: Katarina Valoskova_PhD thesis_final version.pdf file_size: 10054156 relation: main_file file_date_updated: 2021-02-11T11:17:14Z has_accepted_license: '1' language: - iso: eng month: '06' oa: 1 oa_version: Published Version page: '141' 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 publication_identifier: issn: - 2663-337X publication_status: published publisher: Institute of Science and Technology Austria related_material: record: - id: '6187' relation: part_of_dissertation status: public - id: '544' relation: part_of_dissertation status: public status: public supervisor: - first_name: Daria E full_name: Siekhaus, Daria E id: 3D224B9E-F248-11E8-B48F-1D18A9856A87 last_name: Siekhaus orcid: 0000-0001-8323-8353 title: The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration type: dissertation user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 year: '2019' ...