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http://ir.nhri.org.tw/handle/3990099045/5899
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| Title: | A Cullin3-KLHL20 ubiquitin ligase-dependent pathway targets PML to potentiate HIF-1 signaling and prostate cancer progression |
| Authors: | Yuan, WC;Lee, YR;Huang, SF;Lin, YM;Chen, TY;Chung, HC;Tsai, CH;Chen, HY;Chiang, CT;Lai, CK;Lu, LT;Chen, CH;Gu, DL;Pu, YS;Jou, YS;Lu, KP;Hsiao, PW;Shih, HM;Chen, RH |
| Contributors: | Institute of Molecular and Genomic Medicine |
| Abstract: | 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-1 alpha 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-1 alpha, 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-1 alpha autoregulation play key roles in tumor progression. |
| Date: | 2011-08 |
| Relation: | Cancer Cell. 2011 Aug;20(2):214-228. |
| Link to: | http://dx.doi.org/10.1016/j.ccr.2011.07.008 |
| JIF/Ranking 2023: | http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1535-6108&DestApp=IC2JCR |
| Cited Times(WOS): | https://www.webofscience.com/wos/woscc/full-record/WOS:000294099700010 |
| Cited Times(Scopus): | http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=80051583598 |
| Appears in Collections: | [黃秀芬] 期刊論文
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| ISI000294099700010.pdf | | 1762Kb | Adobe PDF | 562 | View/Open |
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