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• W3136575306 abstract "An aberrant accumulation of nuclear β-catenin is closely associated with the augmentation of cancer malignancy. In this work, we report that several microtubule-targeting agents (MTAs) such as vinblastine, taxol, and C12 (combretastatin-2-aminoimidazole analog) inhibit Wnt/β-catenin signaling in oral squamous cell carcinoma (OSCC). We showed that the inhibition of microtubule dynamics by MTAs decreased the level of β-catenin by increasing Axin and adenomatous polyposis coli levels and reducing the level of dishevelled. Furthermore, MTAs strongly reduced the localization of β-catenin in the nucleus. The reduction in the level of nuclear β-catenin was neither due to the degradation of β-catenin in the nucleus nor due to an increase in the export of nuclear β-catenin from the nucleus. A motor protein kinesin-2 was found to assist the nuclear transportation of β-catenin. Interestingly, Wnt/β-catenin signaling antagonist treatment synergized with MTAs and the activators of Wnt/β-catenin signaling antagonized with the MTAs. C12 potently suppressed the growth of 4-Nitroquinoline 1-oxide-induced OSCC in the tongue of C57 black 6 mice and also abrogated Wnt/β-catenin signaling pathway in the tumor. Our results provide evidence that the decrease in Wnt/β-catenin signaling is an important antitumor effect of MTAs and the combined use of MTAs with Wnt/β-catenin signaling antagonists could be a promising strategy for cancer chemotherapy." @default.
• W3136575306 created "2021-03-29" @default.
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• W3136575306 date "2021-03-20" @default.
• W3136575306 modified "2023-10-10" @default.
• W3136575306 title "Microtubule‐targeting agents impair kinesin‐2‐dependent nuclear transport of β‐catenin: Evidence of inhibition of Wnt/β‐catenin signaling as an important antitumor mechanism of microtubule‐targeting agents" @default.
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• W3136575306 doi "https://doi.org/10.1096/fj.202002594r" @default.
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• W3136575306 hasPublicationYear "2021" @default.
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