GSK3β controls epithelial-mesenchymal transition and tumor metastasis by CHIP-mediated degradation of slug

S. H. Kao, W. L. Wang, C. Y. Chen, Y. L. Chang, Y. Y. Wu, Y. T. Wang, S. P. Wang, A. I. Nesvizhskii, Y. J. Chen, T. M. Hong, P. C. Yang

研究成果: Article

65 引文 斯高帕斯(Scopus)

摘要

Glycogen synthase kinase 3 beta (GSK3β) is highly inactivated in epithelial cancers and is known to inhibit tumor migration and invasion. The zinc-finger-containing transcriptional repressor, Slug, represses E-cadherin transcription and enhances epithelial-mesenchymal transition (EMT). In this study, we find that the GSK3β-pSer9 level is associated with the expression of Slug in non-small cell lung cancer. GSK3β-mediated phosphorylation of Slug facilitates Slug protein turnover. Proteomic analysis reveals that the carboxyl terminus of Hsc70-interacting protein (CHIP) interacts with wild-type Slug (wtSlug). Knockdown of CHIP stabilizes the wtSlug protein and reduces Slug ubiquitylation and degradation. In contrast, nonphosphorylatable Slug-4SA is not degraded by CHIP. The accumulation of nondegradable Slug may further lead to the repression of E-cadherin expression and promote cancer cell migration, invasion and metastasis. Our findings provide evidence of a de novo GSK3β-CHIP-Slug pathway that may be involved in the progression of metastasis in lung cancer.

原文English
頁(從 - 到)3172-3182
頁數11
期刊Oncogene
33
發行號24
DOIs
出版狀態Published - 2014 六月 12

    指紋

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

引用此

Kao, S. H., Wang, W. L., Chen, C. Y., Chang, Y. L., Wu, Y. Y., Wang, Y. T., Wang, S. P., Nesvizhskii, A. I., Chen, Y. J., Hong, T. M., & Yang, P. C. (2014). GSK3β controls epithelial-mesenchymal transition and tumor metastasis by CHIP-mediated degradation of slug. Oncogene, 33(24), 3172-3182. https://doi.org/10.1038/onc.2013.279