American Association for Cancer Research
00085472can132712-sup-fig2.pdf (1.87 MB)

Supplementary Figure 2 from YAP-Induced Resistance of Cancer Cells to Antitubulin Drugs Is Modulated by a Hippo-Independent Pathway

Download (1.87 MB)
journal contribution
posted on 2023-03-30, 22:32 authored by Yulei Zhao, Prem Khanal, Paul Savage, Yi-Min She, Terry D. Cyr, Xiaolong Yang

PDF file - 1914KB, Cdk1 is responsible for Taxol-induced TAZ phosphorylation and degradation.



Although antitubulin drugs are used widely to treat human cancer, many patients display intrinsic or acquired drug resistance that imposes major obstacles to successful therapy. Mounting evidence argues that cancer cell apoptosis triggered by antitubulin drugs relies upon activation of the cell-cycle kinase Cdk1; however, mechanistic connections of this event to apoptosis remain obscure. In this study, we identified the antiapoptotic protein YAP, a core component of the Hippo signaling pathway implicated in tumorigenesis, as a critical linker coupling Cdk1 activation to apoptosis in the antitubulin drug response. Antitubulin drugs activated Cdk1, which directly phosphorylated YAP on five sites independent of the Hippo pathway. Mutations in these phosphorylation sites on YAP relieved its ability to block antitubulin drug-induced apoptosis, further suggesting that YAP was inactivated by Cdk1 phosphorylation. Notably, we found that YAP was not phosphorylated and inactivated after antitubulin drug treatment in taxol-resistant cancer cells. Our findings suggest YAP and its phosphorylation status as candidate prognostic markers in predicting antitubulin drug response in patients. Cancer Res; 74(16); 4493–503. ©2014 AACR.

Usage metrics

    Cancer Research