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• W2746461215 abstract "Abstract WWC family proteins negatively regulate HEK 293 cell proliferation and organ growth by suppressing the transcriptional activity of Yes‐associated protein ( YAP ), a major effector of the Hippo pathway. The function of the scaffolding protein WWC 1 (also called KIBRA ) has been intensively studied in cells and animal models. However, the expression and clinicopathologic significance of WWC 2 in cancer are poorly characterized. This study aimed to clarify the biological function and mechanism of action of WWC 2 in hepatocellular carcinoma ( HCC ). Retrospective analysis revealed WWC 2 was significantly down‐regulated in 95 clinical HCC tissues compared to the paired adjacent non‐cancerous tissues. Moreover, loss of WWC 2 expression was significantly associated with advanced clinicopathological features, including venous infiltration, larger tumour size and advanced TNM stage. Positive WWC 2 expression was associated with significantly better 5‐year overall survival, and WWC 2 was an independent prognostic factor for overall survival in HCC . Moreover, we confirmed WWC 2 inhibits HCC cell invasive ability in vitro . Elevated YAP expression was also observed in the same cohort of HCC tissues. Pearson's correlation coefficient analysis indicated WWC 2 expression correlated inversely with nuclear YAP protein expression in HCC . Mechanistically, we confirmed overexpression of WWC 2 suppresses the invasive and metastatic potential of HCC cells by activating large tumour suppressor 1 and 2 kinases ( LATS 1/2), which in turn phosphorylates the transcriptional co‐activator YAP . Overall, this study indicates WWC 2 functions as a tumour suppressor by negatively regulating the Hippo signalling pathway and may serve as a prognostic marker in HCC ." @default.
• W2746461215 created "2017-08-31" @default.
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• W2746461215 date "2017-08-16" @default.
• W2746461215 modified "2023-10-03" @default.
• W2746461215 title "WWC2 is an independent prognostic factor and prevents invasion<i>via</i>Hippo signalling in hepatocellular carcinoma" @default.
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• W2746461215 doi "https://doi.org/10.1111/jcmm.13281" @default.
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