{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Nayak D"],"funding":["American Cancer Society","NCI NIH HHS","National Institutes of Health","NIGMS NIH HHS"],"pagination":["104193"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9036131"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["25(5)"],"pubmed_abstract":["The involvement of membrane-bound solute carriers (SLCs) in neoplastic transdifferentiation processes is poorly defined. Here, we examined changes in the SLC landscape during epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. We show that two SLCs from the organic anion/cation transporter family, SLC22A10 and SLC22A15, favor EMT via interferon (IFN) α and γ signaling activation of receptor tyrosine kinase-like orphan receptor 1 (ROR1) expression. In addition, SLC22A10 and SLC22A15 allow tumor cell accumulation of glutathione to support EMT via the IFNα/γ-ROR1 axis. Moreover, a pan-SLC22A inhibitor lesinurad reduces EMT-induced metastasis and gemcitabine chemoresistance to prolong survival in mouse models of pancreatic cancer, thus identifying new vulnerabilities for human "],"journal":["iScience"],"pubmed_title":["EMT alterations in the solute carrier landscape uncover SLC22A10/A15 imposed vulnerabilities in pancreatic cancer."],"pmcid":["PMC9036131"],"funding_grant_id":["P30 CA016058","R01 GM143217","R01 CA188464"],"pubmed_authors":["Shakya R","Li J","Govindarajan R","Nayak D","Persaud AK","Raj R","Campbell MJ","Weadick B"],"additional_accession":[]},"is_claimable":false,"name":"EMT alterations in the solute carrier landscape uncover SLC22A10/A15 imposed vulnerabilities in pancreatic cancer.","description":"The involvement of membrane-bound solute carriers (SLCs) in neoplastic transdifferentiation processes is poorly defined. Here, we examined changes in the SLC landscape during epithelial-mesenchymal transition (EMT) of pancreatic cancer cells. We show that two SLCs from the organic anion/cation transporter family, SLC22A10 and SLC22A15, favor EMT via interferon (IFN) α and γ signaling activation of receptor tyrosine kinase-like orphan receptor 1 (ROR1) expression. In addition, SLC22A10 and SLC22A15 allow tumor cell accumulation of glutathione to support EMT via the IFNα/γ-ROR1 axis. Moreover, a pan-SLC22A inhibitor lesinurad reduces EMT-induced metastasis and gemcitabine chemoresistance to prolong survival in mouse models of pancreatic cancer, thus identifying new vulnerabilities for human ","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 May","modification":"2026-05-30T15:47:39.35Z","creation":"2025-04-04T10:02:30.269Z"},"accession":"S-EPMC9036131","cross_references":{"pubmed":["35479410"],"doi":["10.1016/j.isci.2022.104193"]}}