p53 controls cancer cell invasion by inducing the MDM2-mediated degradation of Slug

Shu Ping Wang, Wen Lung Wang, Yih Leong Chang, Chen Tu Wu, Yu Chih Chao, Shih Han Kao, Ang Yuan, Chung Wu Lin, Shuenn Chen Yang, Wing Kai Chan, Ker Chau Li, Tse Ming Hong, Pan Chyr Yang

研究成果: Article

284 引文 斯高帕斯(Scopus)

摘要

The tumour suppressor p53 is known to prevent cancer progression by inhibiting proliferation and inducing apoptosis of tumour cells. Slug, an invasion promoter, exerts its effects by repressing E-cadherin transcription. Here we show that wild-type p53 (wtp53) suppresses cancer invasion by inducing Slug degradation, whereas mutant p53 may stabilize Slug protein. In non-small-cell lung cancer (NSCLC), mutation of p53 correlates with low MDM2, high Slug and low E-cadherin expression. This expression profile is associated with poor overall survival and short metastasis-free survival in patients with NSCLC. wtp53 upregulates MDM2 and forms a wtp53-MDM2-Slug complex that facilitates MDM2-mediated Slug degradation. Downregulation of Slug by wtp53 or MDM2 enhances E-cadherin expression and represses cancer cell invasiveness. In contrast, mutant p53 inactivates Slug degradation and leads to Slug accumulation and increased cancer cell invasiveness. Our findings indicate that wtp53 and p53 mutants may differentially control cancer invasion and metastasis through the p53-MDM2-Slug pathway.

原文English
頁(從 - 到)694-704
頁數11
期刊Nature Cell Biology
11
發行號6
DOIs
出版狀態Published - 2009 五月 18

    指紋

All Science Journal Classification (ASJC) codes

  • Cell Biology

引用此

Wang, S. P., Wang, W. L., Chang, Y. L., Wu, C. T., Chao, Y. C., Kao, S. H., Yuan, A., Lin, C. W., Yang, S. C., Chan, W. K., Li, K. C., Hong, T. M., & Yang, P. C. (2009). p53 controls cancer cell invasion by inducing the MDM2-mediated degradation of Slug. Nature Cell Biology, 11(6), 694-704. https://doi.org/10.1038/ncb1875