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Accession IconGSE92919

A UBE2O-AMPK2 axis that promotes tumor initiation and progression offers opportunities for therapy

Organism Icon Mus musculus
Sample Icon 6 Downloadable Samples
Technology Badge IconIllumina MouseWG-6 v2.0 R2 expression beadchip

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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 AMPK2 for ubiquitination and degradation, and thereby promotes activation of the mTOR-HIF1 pathway. Notably, inactivation of AMPK2, but not AMPK1, 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 AMPK2, suggesting the UBE2O-AMPK2 axis as a potential cancer therapeutic target.
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