| Literature DB >> 28162974 |
Isabelle K Vila1, Yixin Yao1, Goeun Kim2, Weiya Xia1, Hyejin Kim1, Sun-Joong Kim1, Mi-Kyung Park1, James P Hwang1, Enrique González-Billalabeitia3, Mien-Chie Hung4, Su Jung Song5, Min Sup Song6.
Abstract
UBE2O is localized in the 17q25 locus, which is known to be amplified in human cancers, but its role in tumorigenesis remains undefined. Here we show that Ube2o deletion in MMTV-PyVT or TRAMP mice profoundly impairs tumor initiation, growth, and metastasis, while switching off the metabolic reprogramming of tumor cells. Mechanistically, UBE2O specifically targets AMPKα2 for ubiquitination and degradation, and thereby promotes activation of the mTOR-HIF1α pathway. Notably, inactivation of AMPKα2, but not AMPKα1, abrogates the tumor attenuation caused by UBE2O loss, while treatment with rapamycin or inhibition of HIF1α ablates UBE2O-dependent tumor biology. Finally, pharmacological blockade of UBE2O inhibits tumorigenesis through the restoration of AMPKα2, suggesting the UBE2O-AMPKα2 axis as a potential cancer therapeutic target.Entities:
Keywords: AMPK; AMPKα2; HIF1α; UBE2O; arsenite; breast cancer; cancer metabolism; mTOR; prostate cancer; ubiquitination
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Year: 2017 PMID： 28162974 PMCID： PMC5463996 DOI： 10.1016/j.ccell.2017.01.003
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743