biostudies-literatureBoichuk SRussian Science Foundation8138https://www.ebi.ac.uk/biostudies/studies/S-EPMC12428531biostudies-literatureUnknown26(17)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 ceInternational journal of molecular sciencesClaudin-1 Contributes to Gastrointestinal Stromal Tumors (GIST) Resistance to Imatinib Mesylate (IM) via Regulation of FGFR-Signaling.PMC1242853124-25-00418Dunaev PValeeva EMikheeva ESabirov AKhromova NMani SShagimardanova EShigapova LRyzhkin SDeviatiiarov RGalembikova ABikinieva FKopnin PBoichuk SfalseClaudin-1 Contributes to Gastrointestinal Stromal Tumors (GIST) Resistance to Imatinib Mesylate (IM) via Regulation of FGFR-Signaling.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 ce2025-01-01T00:00:00Z2025 Aug2026-04-23T03:21:36.122Z2026-04-23T03:11:43.955ZS-EPMC124285314094306810.3390/ijms26178138