[{"language":[{"iso":"eng"}],"article_number":"777634","month":"02","project":[{"name":"Investigating the role of the novel major superfamily facilitator transporter family member MFSD1 in metastasis","grant_number":"LSC16-021 ","_id":"2637E9C0-B435-11E9-9278-68D0E5697425"}],"oa_version":"Published Version","acknowledged_ssus":[{"_id":"Bio"}],"has_accepted_license":"1","publication":"Frontiers in Oncology","status":"public","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","related_material":{"link":[{"url":"https://ist.ac.at/en/news/suppressing-the-spread-of-tumors/","description":"News on IST Homepage","relation":"confirmation"}]},"file":[{"date_created":"2022-02-08T13:26:40Z","file_size":6303227,"checksum":"63dfecf30c5bbf9408b3512bd603f78c","date_updated":"2022-02-08T13:26:40Z","file_name":"2022_FrontiersOncol_Roblek.pdf","content_type":"application/pdf","access_level":"open_access","success":1,"relation":"main_file","file_id":"10751","creator":"cchlebak"}],"oa":1,"publication_identifier":{"issn":["2234-943X"]},"type":"journal_article","date_published":"2022-02-08T00:00:00Z","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"article_type":"original","publisher":"Frontiers","file_date_updated":"2022-02-08T13:26:40Z","quality_controlled":"1","intvolume":"        12","title":"The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis","department":[{"_id":"DaSi"}],"date_created":"2022-02-01T10:33:50Z","article_processing_charge":"Yes (via OA deal)","publication_status":"published","author":[{"last_name":"Roblek","first_name":"Marko","full_name":"Roblek, Marko","orcid":"0000-0001-9588-1389","id":"3047D808-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Bicher, Julia","first_name":"Julia","last_name":"Bicher","id":"3CCBB46E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Merel","last_name":"van Gogh","full_name":"van Gogh, Merel"},{"first_name":"Attila","last_name":"György","orcid":"0000-0002-1819-198X","full_name":"György, Attila","id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Seeböck, Rita","first_name":"Rita","last_name":"Seeböck"},{"first_name":"Bozena","last_name":"Szulc","full_name":"Szulc, Bozena"},{"full_name":"Damme, Markus","last_name":"Damme","first_name":"Markus"},{"first_name":"Mariusz","last_name":"Olczak","full_name":"Olczak, Mariusz"},{"first_name":"Lubor","last_name":"Borsig","full_name":"Borsig, Lubor"},{"first_name":"Daria E","last_name":"Siekhaus","orcid":"0000-0001-8323-8353","full_name":"Siekhaus, Daria E","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87"}],"scopus_import":"1","_id":"10712","ddc":["570"],"volume":12,"acknowledgement":"We thank M. Sixt, A. Leithner, and J. Alanko for helpful advice and the BioImaging Facility at IST Austria for technical support and assistance. We thank the Siekhaus Lab for the careful review of the manuscript and their input. MR and DS were funded by the NO Forschungs- und Bildungsges.m.b.H. (LS16-021) and IST core funding. MD was funded by Deutsche Forschungsgemeinschaft (DA 1785-1).","abstract":[{"text":"Solute carriers are increasingly recognized as participating in a plethora of pathologies, including cancer. We describe here the involvement of the orphan solute carrier MFSD1 in the regulation of tumor cell migration. Loss of MFSD1 enabled higher levels of metastasis in a mouse model. We identified an increased migratory potential in MFSD1-/- tumor cells which was mediated by increased focal adhesion turn-over, reduced stability of mature inactive β1 integrin, and the resulting increased integrin activation index. We show that MFSD1 promoted recycling to the cell surface of endocytosed inactive β1 integrin and thereby protected β1 integrin from proteolytic degradation; this led to dampening of the integrin activation index. Furthermore, down-regulation of MFSD1 expression was observed during early steps of tumorigenesis and higher MFSD1 expression levels correlate with a better cancer patient prognosis. In sum, we describe a requirement for endolysosomal MFSD1 in efficient β1 integrin recycling to suppress tumor spread.","lang":"eng"}],"day":"08","doi":"10.3389/fonc.2022.777634","external_id":{"isi":["000760618800001"]},"isi":1,"citation":{"apa":"Roblek, M., Bicher, J., van Gogh, M., György, A., Seeböck, R., Szulc, B., … Siekhaus, D. E. (2022). The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis. <i>Frontiers in Oncology</i>. Frontiers. <a href=\"https://doi.org/10.3389/fonc.2022.777634\">https://doi.org/10.3389/fonc.2022.777634</a>","ama":"Roblek M, Bicher J, van Gogh M, et al. The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis. <i>Frontiers in Oncology</i>. 2022;12. doi:<a href=\"https://doi.org/10.3389/fonc.2022.777634\">10.3389/fonc.2022.777634</a>","chicago":"Roblek, Marko, Julia Bicher, Merel van Gogh, Attila György, Rita Seeböck, Bozena Szulc, Markus Damme, Mariusz Olczak, Lubor Borsig, and Daria E Siekhaus. “The Solute Carrier MFSD1 Decreases Β1 Integrin’s Activation Status and Thus Tumor Metastasis.” <i>Frontiers in Oncology</i>. Frontiers, 2022. <a href=\"https://doi.org/10.3389/fonc.2022.777634\">https://doi.org/10.3389/fonc.2022.777634</a>.","ieee":"M. Roblek <i>et al.</i>, “The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis,” <i>Frontiers in Oncology</i>, vol. 12. Frontiers, 2022.","short":"M. Roblek, J. Bicher, M. van Gogh, A. György, R. Seeböck, B. Szulc, M. Damme, M. Olczak, L. Borsig, D.E. Siekhaus, Frontiers in Oncology 12 (2022).","mla":"Roblek, Marko, et al. “The Solute Carrier MFSD1 Decreases Β1 Integrin’s Activation Status and Thus Tumor Metastasis.” <i>Frontiers in Oncology</i>, vol. 12, 777634, Frontiers, 2022, doi:<a href=\"https://doi.org/10.3389/fonc.2022.777634\">10.3389/fonc.2022.777634</a>.","ista":"Roblek M, Bicher J, van Gogh M, György A, Seeböck R, Szulc B, Damme M, Olczak M, Borsig L, Siekhaus DE. 2022. The solute carrier MFSD1 decreases β1 integrin’s activation status and thus tumor metastasis. Frontiers in Oncology. 12, 777634."},"year":"2022","date_updated":"2023-08-02T14:05:44Z"},{"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)"},"type":"journal_article","date_published":"2022-08-25T00:00:00Z","publication_identifier":{"issn":["2234-943X"]},"oa":1,"file":[{"success":1,"relation":"main_file","access_level":"open_access","creator":"dernst","file_id":"12450","checksum":"efc7edf9f626af31853790c5b598a68c","file_size":13588502,"date_created":"2023-01-30T10:25:21Z","file_name":"2022_FrontiersOntology_Basilico.pdf","content_type":"application/pdf","date_updated":"2023-01-30T10:25:21Z"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","status":"public","has_accepted_license":"1","publication":"Frontiers in Oncology","oa_version":"Published Version","article_number":"983507","month":"08","keyword":["Cancer Research","Oncology"],"language":[{"iso":"eng"}],"year":"2022","citation":{"short":"B. Basilico, I.E. Palamà, S. D’Amone, C. Lauro, M. Rosito, M. Grieco, P. Ratano, F. Cordella, C. Sanchini, S. Di Angelantonio, D. Ragozzino, M. Cascione, G. Gigli, B. Cortese, Frontiers in Oncology 12 (2022).","mla":"Basilico, Bernadette, et al. “Substrate Stiffness Effect on Molecular Crosstalk of Epithelial-Mesenchymal Transition Mediators of Human Glioblastoma Cells.” <i>Frontiers in Oncology</i>, vol. 12, 983507, Frontiers Media, 2022, doi:<a href=\"https://doi.org/10.3389/fonc.2022.983507\">10.3389/fonc.2022.983507</a>.","ista":"Basilico B, Palamà IE, D’Amone S, Lauro C, Rosito M, Grieco M, Ratano P, Cordella F, Sanchini C, Di Angelantonio S, Ragozzino D, Cascione M, Gigli G, Cortese B. 2022. Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells. Frontiers in Oncology. 12, 983507.","ama":"Basilico B, Palamà IE, D’Amone S, et al. Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells. <i>Frontiers in Oncology</i>. 2022;12. doi:<a href=\"https://doi.org/10.3389/fonc.2022.983507\">10.3389/fonc.2022.983507</a>","apa":"Basilico, B., Palamà, I. E., D’Amone, S., Lauro, C., Rosito, M., Grieco, M., … Cortese, B. (2022). Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells. <i>Frontiers in Oncology</i>. Frontiers Media. <a href=\"https://doi.org/10.3389/fonc.2022.983507\">https://doi.org/10.3389/fonc.2022.983507</a>","ieee":"B. Basilico <i>et al.</i>, “Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells,” <i>Frontiers in Oncology</i>, vol. 12. Frontiers Media, 2022.","chicago":"Basilico, Bernadette, Ilaria Elena Palamà, Stefania D’Amone, Clotilde Lauro, Maria Rosito, Maddalena Grieco, Patrizia Ratano, et al. “Substrate Stiffness Effect on Molecular Crosstalk of Epithelial-Mesenchymal Transition Mediators of Human Glioblastoma Cells.” <i>Frontiers in Oncology</i>. Frontiers Media, 2022. <a href=\"https://doi.org/10.3389/fonc.2022.983507\">https://doi.org/10.3389/fonc.2022.983507</a>."},"date_updated":"2023-08-04T09:54:16Z","external_id":{"isi":["000856524900001"],"pmid":["36091138"]},"isi":1,"day":"25","doi":"10.3389/fonc.2022.983507","abstract":[{"lang":"eng","text":"The complexity of the microenvironment effects on cell response, show accumulating evidence that glioblastoma (GBM) migration and invasiveness are influenced by the mechanical rigidity of their surroundings. The epithelial–mesenchymal transition (EMT) is a well-recognized driving force of the invasive behavior of cancer. However, the primary mechanisms of EMT initiation and progression remain unclear. We have previously showed that certain substrate stiffness can selectively stimulate human GBM U251-MG and GL15 glioblastoma cell lines motility. The present study unifies several known EMT mediators to uncover the reason of the regulation and response to these stiffnesses. Our results revealed that changing the rigidity of the mechanical environment tuned the response of both cell lines through change in morphological features, epithelial-mesenchymal markers (E-, N-Cadherin), EGFR and ROS expressions in an interrelated manner. Specifically, a stiffer microenvironment induced a mesenchymal cell shape, a more fragmented morphology, higher intracellular cytosolic ROS expression and lower mitochondrial ROS. Finally, we observed that cells more motile showed a more depolarized mitochondrial membrane potential. Unravelling the process that regulates GBM cells’ infiltrative behavior could provide new opportunities for identification of new targets and less invasive approaches for treatment."}],"acknowledgement":"The research leading to these results has received funding from AIRC under IG 2021 - ID. 26328 project – P.I. Cortese Barbara and AIRC under MFAG 2015 - ID. 16803 project – “P.I. Cortese Barbara”. The authors are also grateful to the ”Tecnopolo per la medicina di precisione” (TecnoMed Puglia) - Regione Puglia: DGR n.2117 del 21/11/2018, CUP: B84I18000540002 and “Tecnopolo di Nanotecnologia e Fotonica per la medicina di precisione” (TECNOMED) - FISR/MIUR-CNR: delibera CIPE n.3449 del 7-08-2017, CUP: B83B17000010001.\r\nWe thank Dr. Francesca Pagani for useful technical support. We thank also Irene Iacuitto, Giovanna Loffredo and Manuela Marchetti for practical administrative support.","volume":12,"ddc":["570"],"scopus_import":"1","_id":"12268","pmid":1,"author":[{"id":"36035796-5ACA-11E9-A75E-7AF2E5697425","full_name":"Basilico, Bernadette","orcid":"0000-0003-1843-3173","last_name":"Basilico","first_name":"Bernadette"},{"last_name":"Palamà","first_name":"Ilaria Elena","full_name":"Palamà, Ilaria Elena"},{"last_name":"D’Amone","first_name":"Stefania","full_name":"D’Amone, Stefania"},{"first_name":"Clotilde","last_name":"Lauro","full_name":"Lauro, Clotilde"},{"last_name":"Rosito","first_name":"Maria","full_name":"Rosito, Maria"},{"last_name":"Grieco","first_name":"Maddalena","full_name":"Grieco, Maddalena"},{"full_name":"Ratano, Patrizia","first_name":"Patrizia","last_name":"Ratano"},{"last_name":"Cordella","first_name":"Federica","full_name":"Cordella, Federica"},{"full_name":"Sanchini, Caterina","last_name":"Sanchini","first_name":"Caterina"},{"first_name":"Silvia","last_name":"Di Angelantonio","full_name":"Di Angelantonio, Silvia"},{"full_name":"Ragozzino, Davide","last_name":"Ragozzino","first_name":"Davide"},{"full_name":"Cascione, Mariafrancesca","first_name":"Mariafrancesca","last_name":"Cascione"},{"first_name":"Giuseppe","last_name":"Gigli","full_name":"Gigli, Giuseppe"},{"full_name":"Cortese, Barbara","first_name":"Barbara","last_name":"Cortese"}],"department":[{"_id":"GaNo"}],"date_created":"2023-01-16T10:00:28Z","article_processing_charge":"No","publication_status":"published","intvolume":"        12","title":"Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells","quality_controlled":"1","file_date_updated":"2023-01-30T10:25:21Z","publisher":"Frontiers Media","article_type":"original"}]