A Cullin3-KLHL20 Ubiquitin Ligase-Dependent Pathway Targets PML to Potentiate HIF-1 Signaling and Prostate Cancer Progression

Wei Chien Yuan, Yu Ru Lee, Shiu Feng Huang, Yu Min Lin, Tzu Yin Chen, Hsiang Ching Chung, Chin Hsien Tsai, Hsin Yi Chen, Cheng Ta Chiang, Chun Kai Lai, Li Ting Lu, Chun Hau Chen, De Leung Gu, Yeong Shiau Pu, Yuh Shan Jou, Kun Ping Lu, Pei Wen Hsiao, Hsiu Ming Shih, Ruey Hwa Chen

研究成果: 雜誌貢獻文章

93 引文 斯高帕斯(Scopus)

摘要

Tumor hypoxia is associated with disease progression and treatment failure, but the hypoxia signaling mechanism is not fully understood. Here, we show that KLHL20, a Cullin3 (Cul3) substrate adaptor induced by HIF-1, coordinates with the actions of CDK1/2 and Pin1 to mediate hypoxia-induced PML proteasomal degradation. Furthermore, this PML destruction pathway participates in a feedback mechanism to maximize HIF-1α induction, thereby potentiating multiple tumor hypoxia responses, including metabolic reprogramming, epithelial-mesenchymal transition, migration, tumor growth, angiogenesis, and chemoresistance. In human prostate cancer, overexpression of HIF-1α, KLHL20, and Pin1 correlates with PML down-regulation, and hyperactivation of the PML destruction pathway is associated with disease progression. Our study indicates that the KLHL20-mediated PML degradation and HIF-1α autoregulation play key roles in tumor progression.
原文英語
頁(從 - 到)214-228
頁數15
期刊Cancer Cell
20
發行號2
DOIs
出版狀態已發佈 - 八月 16 2011
對外發佈Yes

    指紋

ASJC Scopus subject areas

  • Cancer Research
  • Cell Biology
  • Oncology

引用此

Yuan, W. C., Lee, Y. R., Huang, S. F., Lin, Y. M., Chen, T. Y., Chung, H. C., Tsai, C. H., Chen, H. Y., Chiang, C. T., Lai, C. K., Lu, L. T., Chen, C. H., Gu, D. L., Pu, Y. S., Jou, Y. S., Lu, K. P., Hsiao, P. W., Shih, H. M., & Chen, R. H. (2011). A Cullin3-KLHL20 Ubiquitin Ligase-Dependent Pathway Targets PML to Potentiate HIF-1 Signaling and Prostate Cancer Progression. Cancer Cell, 20(2), 214-228. https://doi.org/10.1016/j.ccr.2011.07.008