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A UBE2O-AMPK?2 Axis that Promotes Tumor Initiation and Progression Offers Opportunities for Therapy.

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 AMPK?2 for ubiquitination and degradation, and thereby promotes activation of the mTOR-HIF1? pathway. Notably, inactivation of AMPK?2, but not AMPK?1, abrogates the tumor attenuation caused by UBE2O loss, while treatment with rapamycin or inhibition of HIF1? ablates UBE2O-dependent tumor biology. Finally, pharmacological blockade of UBE2O inhibits tumorigenesis through the restoration of AMPK?2, suggesting the UBE2O-AMPK?2 axis as a potential cancer therapeutic target.

SUBMITTER: Vila IK

PROVIDER: S-EPMC5463996 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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A UBE2O-AMPKα2 Axis that Promotes Tumor Initiation and Progression Offers Opportunities for Therapy.

Vila Isabelle K IK Yao Yixin Y Kim Goeun G Xia Weiya W Kim Hyejin H Kim Sun-Joong SJ Park Mi-Kyung MK Hwang James P JP González-Billalabeitia Enrique E Hung Mien-Chie MC Song Su Jung SJ Song Min Sup MS

Cancer cell 20170202 2

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, ...[more]

PMID: 28162974

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Dataset Information

A UBE2O-AMPK?2 Axis that Promotes Tumor Initiation and Progression Offers Opportunities for Therapy.

Publications

A UBE2O-AMPKα2 Axis that Promotes Tumor Initiation and Progression Offers Opportunities for Therapy.

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