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• W4302287325 abstract "XPO1 mediates the nuclear export of several proteins, mainly tumor suppressors. KPT-330 (Selinexor) is a selective inhibitor of XPO1 that has demonstrated good therapeutic effects in hematologic cancers.We used TCGA and GTEx pan-cancer database to evaluate XPO1 mRNA expression in various tumors. Cell proliferation assay and colony formation assay were used to analyze the in vitro antitumor effects of XPO1 inhibitor KPT-330. Western blot was performed to explore the specific mechanisms.We found that XPO1 was highly expressed across a range of cancers and associated with poor prognosis in hepatobiliary and pancreatic tumors. We revealed that the XPO1 inhibitor KPT-330 triggered the nuclear accumulation of the p53 protein and significantly disrupted the proliferation of cholangiocarcinoma cells. Mechanistically, the XPO1 inhibitor, KPT-330, reduced BIRC6 expression by inhibiting the PI3K/AKT pathway to decrease p53 degradation and improve its stability.Therefore, XPO1 may be a potential therapeutic target in cholangiocarcinoma, mediated by its effects on KPT-330." @default.
• W4302287325 created "2022-10-06" @default.
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• W4302287325 date "2022-10-05" @default.
• W4302287325 modified "2023-10-16" @default.
• W4302287325 title "Inhibition of XPO1 impairs cholangiocarcinoma cell proliferation by triggering p53 intranuclear accumulation" @default.
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• W4302287325 doi "https://doi.org/10.1002/cam4.5322" @default.
• W4302287325 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/36200270" @default.
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