ERRα augments HIF‐1 signalling by directly interacting with HIF‐1α in normoxic and hypoxic prostate cancer cells

• DOI: 10.1002/path.4329
• Publication Date: 2014-01-15T08:40:40Z
• Authors: Chang Zou; Shan Yu; Zhenyu Xu; Dinglan Wu; Chi‐Fai Ng; Xiaoqiang Yao; David T Yew; Jean‐Marc Vanacker; Franky L Chan
• Keywords: Cellular adaptation; Hypoxia; Hypoxia-Inducible Factors; Reprogramming

Abstract Adaptation of cancer cells to a hypoxic microenvironment is important for their facilitated malignant growth and advanced development. One major mechanism mediating the response involves up‐regulation hypoxia‐inducible factor 1 ( HIF ‐1) expression, which controls reprogramming energy metabolism angiogenesis. Oestrogen‐related receptor‐ α ERR ) pivotal regulator cellular many biosynthetic pathways, has also been proposed be an promoting Warburg effect in cancer. We others have previously shown that expression increased prostate prognostic marker. Here we show oncogenic key regulator. ‐over‐expressing were more resistant hypoxia showed enhanced ‐1 protein signalling. These effects could observed grown under normoxia, suggesting function pre‐adapt meet stress. Immunoprecipitation FRET assays indicated physically interact with via its AF ‐2 domain. A ubiquitination assay this – interaction inhibit thus reduce degradation. Such attenuated by XCT790 , ‐specific inverse agonist, resulting reduced levels. In summary, can promote adaptation protective as potential therapeutic target treatment. Copyright © 2014 Pathological Society Great Britain Ireland. Published John Wiley & Sons, Ltd.