{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Boichuk S"],"funding":["Russian Science Foundation"],"pagination":["8138"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12428531"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["26(17)"],"pubmed_abstract":["We previously demonstrated that the activation of FGFR signaling in GIST may be a mechanism of GIST resistance to imatinib mesylate (IM). We show here that IM-resistant GIST cells lacking secondary <i>KIT</i> mutations overexpress claudin-1 on both transcriptional and translational levels. In contrast, a knockdown of <i>CLDN1</i> or inhibition of its activity by PDS-0330 effectively restored GIST's sensitivity to IM both in vitro and in vivo. This was evidenced by the increased expression of apoptotic markers (e.g., cleaved PARP and caspase-3) and the decreased proliferation rate of IM-resistant GIST T-1R cells treated with a combination of IM and PDS-0330 (or siRNA <i>CLDN1</i>). In concordance with these findings, a significant synergy was observed between IM and PDS-0330 in GIST T-1R ce"],"journal":["International journal of molecular sciences"],"pubmed_title":["Claudin-1 Contributes to Gastrointestinal Stromal Tumors (GIST) Resistance to Imatinib Mesylate (IM) via Regulation of FGFR-Signaling."],"pmcid":["PMC12428531"],"funding_grant_id":["24-25-00418"],"pubmed_authors":["Dunaev P","Valeeva E","Mikheeva E","Sabirov A","Khromova N","Mani S","Shagimardanova E","Shigapova L","Ryzhkin S","Deviatiiarov R","Galembikova A","Bikinieva F","Kopnin P","Boichuk S"],"additional_accession":[]},"is_claimable":false,"name":"Claudin-1 Contributes to Gastrointestinal Stromal Tumors (GIST) Resistance to Imatinib Mesylate (IM) via Regulation of FGFR-Signaling.","description":"We previously demonstrated that the activation of FGFR signaling in GIST may be a mechanism of GIST resistance to imatinib mesylate (IM). We show here that IM-resistant GIST cells lacking secondary <i>KIT</i> mutations overexpress claudin-1 on both transcriptional and translational levels. In contrast, a knockdown of <i>CLDN1</i> or inhibition of its activity by PDS-0330 effectively restored GIST's sensitivity to IM both in vitro and in vivo. This was evidenced by the increased expression of apoptotic markers (e.g., cleaved PARP and caspase-3) and the decreased proliferation rate of IM-resistant GIST T-1R cells treated with a combination of IM and PDS-0330 (or siRNA <i>CLDN1</i>). In concordance with these findings, a significant synergy was observed between IM and PDS-0330 in GIST T-1R ce","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Aug","modification":"2026-04-23T03:21:36.122Z","creation":"2026-04-23T03:11:43.955Z"},"accession":"S-EPMC12428531","cross_references":{"pubmed":["40943068"],"doi":["10.3390/ijms26178138"]}}