| First Author | Vila IK | Year | 2017 |
| Journal | Cancer Cell | Volume | 31 |
| Issue | 2 | Pages | 208-224 |
| PubMed ID | 28162974 | Mgi Jnum | J:239679 |
| Mgi Id | MGI:5829495 | Doi | 10.1016/j.ccell.2017.01.003 |
| Citation | Vila IK, et al. (2017) A UBE2O-AMPKalpha2 Axis that Promotes Tumor Initiation and Progression Offers Opportunities for Therapy. Cancer Cell 31(2):208-224 |
| abstractText | 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 AMPKalpha2 for ubiquitination and degradation, and thereby promotes activation of the mTOR-HIF1alpha pathway. Notably, inactivation of AMPKalpha2, but not AMPKalpha1, abrogates the tumor attenuation caused by UBE2O loss, while treatment with rapamycin or inhibition of HIF1alpha ablates UBE2O-dependent tumor biology. Finally, pharmacological blockade of UBE2O inhibits tumorigenesis through the restoration of AMPKalpha2, suggesting the UBE2O-AMPKalpha2 axis as a potential cancer therapeutic target. |
