[{"year":"2019","_id":"6187","abstract":[{"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.","lang":"eng"}],"date_updated":"2024-03-25T23:30:15Z","month":"03","type":"journal_article","oa_version":"Published Version","volume":8,"file_date_updated":"2020-07-14T12:47:23Z","date_created":"2019-03-28T13:37:45Z","external_id":{"isi":["000462530200001"]},"status":"public","intvolume":"         8","related_material":{"record":[{"relation":"dissertation_contains","id":"6530"},{"status":"public","id":"8983","relation":"dissertation_contains"},{"relation":"dissertation_contains","status":"public","id":"6546"}],"link":[{"url":"https://ist.ac.at/en/news/new-gene-potentially-involved-in-metastasis-identified/","description":"News on IST Homepage","relation":"press_release"}]},"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. <i>eLife</i>. 2019;8. doi:<a href=\"https://doi.org/10.7554/elife.41801\">10.7554/elife.41801</a>","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.” <i>ELife</i>, vol. 8, e41801, eLife Sciences Publications, 2019, doi:<a href=\"https://doi.org/10.7554/elife.41801\">10.7554/elife.41801</a>.","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. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.41801\">https://doi.org/10.7554/elife.41801</a>","ieee":"K. Valosková <i>et al.</i>, “A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion,” <i>eLife</i>, vol. 8. eLife Sciences Publications, 2019.","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.” <i>ELife</i>. eLife Sciences Publications, 2019. <a href=\"https://doi.org/10.7554/elife.41801\">https://doi.org/10.7554/elife.41801</a>.","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)."},"oa":1,"publication_status":"published","has_accepted_license":"1","date_published":"2019-03-26T00:00:00Z","ddc":["570"],"acknowledged_ssus":[{"_id":"LifeSc"}],"publisher":"eLife Sciences Publications","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"DaSi"}],"publication":"eLife","article_processing_charge":"No","scopus_import":"1","ec_funded":1,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"author":[{"first_name":"Katarina","last_name":"Valosková","full_name":"Valosková, Katarina","id":"46F146FC-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Biebl, Julia","id":"3CCBB46E-F248-11E8-B48F-1D18A9856A87","first_name":"Julia","last_name":"Biebl"},{"last_name":"Roblek","first_name":"Marko","full_name":"Roblek, Marko","id":"3047D808-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-9588-1389"},{"full_name":"Emtenani, Shamsi","id":"49D32318-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6981-6938","first_name":"Shamsi","last_name":"Emtenani"},{"full_name":"György, Attila","orcid":"0000-0002-1819-198X","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","last_name":"György","first_name":"Attila"},{"id":"495A3C32-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2427-6856","full_name":"Misova, Michaela","first_name":"Michaela","last_name":"Misova"},{"full_name":"Ratheesh, Aparna","id":"2F064CFE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7190-0776","last_name":"Ratheesh","first_name":"Aparna"},{"id":"2CE4065A-F248-11E8-B48F-1D18A9856A87","full_name":"Rodrigues, Patricia","last_name":"Rodrigues","first_name":"Patricia"},{"full_name":"Shkarina, Katerina","last_name":"Shkarina","first_name":"Katerina"},{"last_name":"Larsen","first_name":"Ida Signe Bohse","full_name":"Larsen, Ida Signe Bohse"},{"full_name":"Vakhrushev, Sergey Y","last_name":"Vakhrushev","first_name":"Sergey Y"},{"first_name":"Henrik","last_name":"Clausen","full_name":"Clausen, Henrik"},{"last_name":"Siekhaus","first_name":"Daria E","full_name":"Siekhaus, Daria E","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8323-8353"}],"file":[{"creator":"dernst","content_type":"application/pdf","relation":"main_file","file_size":4496017,"file_name":"2019_eLife_Valoskova.pdf","access_level":"open_access","date_created":"2019-03-28T14:00:41Z","checksum":"cc0d1a512559d52e7e7cb0e9b9854b40","date_updated":"2020-07-14T12:47:23Z","file_id":"6188"}],"day":"26","title":"A conserved major facilitator superfamily member orchestrates a subset of O-glycosylation to aid macrophage tissue invasion","article_number":"e41801","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"},{"_id":"253B6E48-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"The role of Drosophila TNF alpha in immune cell invasion","grant_number":"P29638"},{"grant_number":"334077","call_identifier":"FP7","_id":"2536F660-B435-11E9-9278-68D0E5697425","name":"Investigating the role of transporters in invasive migration through junctions"},{"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","call_identifier":"FP7","grant_number":"329540"},{"name":"International IST Doctoral Program","call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385"}],"isi":1,"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2050-084X"]},"doi":"10.7554/elife.41801","quality_controlled":"1"},{"supervisor":[{"id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8323-8353","full_name":"Siekhaus, Daria E","last_name":"Siekhaus","first_name":"Daria E"}],"ddc":["570"],"date_published":"2019-06-07T00:00:00Z","acknowledged_ssus":[{"_id":"Bio"}],"oa":1,"publication_status":"published","has_accepted_license":"1","related_material":{"record":[{"status":"public","id":"6187","relation":"part_of_dissertation"},{"relation":"part_of_dissertation","id":"544","status":"public"}]},"citation":{"ama":"Valosková K. The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration. 2019. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6546\">10.15479/AT:ISTA:6546</a>","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. <i>The Role of a Highly Conserved Major Facilitator Superfamily Member in Drosophila Embryonic Macrophage Migration</i>. Institute of Science and Technology Austria, 2019, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6546\">10.15479/AT:ISTA:6546</a>.","apa":"Valosková, K. (2019). <i>The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:6546\">https://doi.org/10.15479/AT:ISTA:6546</a>","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.","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. <a href=\"https://doi.org/10.15479/AT:ISTA:6546\">https://doi.org/10.15479/AT:ISTA:6546</a>.","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."},"alternative_title":["ISTA Thesis"],"status":"public","date_created":"2019-06-07T12:49:19Z","file_date_updated":"2021-02-11T11:17:14Z","page":"141","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"}],"date_updated":"2023-09-19T10:15:54Z","month":"06","type":"dissertation","oa_version":"Published Version","_id":"6546","year":"2019","doi":"10.15479/AT:ISTA:6546","publication_identifier":{"issn":["2663-337X"]},"language":[{"iso":"eng"}],"project":[{"name":"Examination of the role of a MFS transporter in the migration of Drosophila immune cells","_id":"253CDE40-B435-11E9-9278-68D0E5697425","grant_number":"24283"}],"title":"The role of a highly conserved major facilitator superfamily member in Drosophila embryonic macrophage migration","degree_awarded":"PhD","author":[{"full_name":"Valosková, Katarina","id":"46F146FC-F248-11E8-B48F-1D18A9856A87","first_name":"Katarina","last_name":"Valosková"}],"file":[{"file_name":"Katarina Valoskova_PhD thesis_final version.docx","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","relation":"source_file","file_size":14110626,"creator":"khribikova","embargo_to":"open_access","date_updated":"2020-07-14T12:47:33Z","file_id":"6549","checksum":"68949c2d96210b45b981a23e9c9cd93c","date_created":"2019-06-07T13:00:04Z","access_level":"closed"},{"date_created":"2019-06-07T13:00:08Z","access_level":"open_access","file_id":"6550","date_updated":"2021-02-11T11:17:14Z","checksum":"555329cd76e196c96f5278c480ee2e6e","file_size":10054156,"content_type":"application/pdf","embargo":"2020-06-07","relation":"main_file","creator":"khribikova","file_name":"Katarina Valoskova_PhD thesis_final version.pdf"}],"day":"07","article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publisher":"Institute of Science and Technology Austria","department":[{"_id":"DaSi"}]}]