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.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5463996 | PMC |
| http://dx.doi.org/10.1016/j.ccell.2017.01.003 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Jejunal Artery Aneurysm Exclusion With Immediate Vascular Reconstruction: A Case Report.
Port J Card Thorac Vasc Surg
January 2025
Angiology and Vascular Surgery, Unidade Local de Saúde de São João; Surgery and Physiology, Faculdade de Medicina da Universidade do Porto, Portugal.
A 44 year-old previously healthy woman presented a persistent epigastric pain. Computed tomography revealed a saccular aneurysm with a diameter of 25x20 mm in the first jejunal artery and also a stenosis in the celiac trunk associated with median arcuate ligament syndrome, turning the hepatic perfusion dependent of the gastroduodenal artery flow. Through a midline laparotomy, celiac axis was exposed, and median arcuate ligament released for median arcuate ligament syndrome treatment.
View Article and Find Full Text PDFTRAF1 promotes osteoclastogenesis by enhancing metabolic adaptation to oxidative phosphorylation in an AKT-dependent manner.
Mol Ther
January 2025
Department of Orthopaedic surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address:
Tumor necrosis factor receptor-associated factor 1 (TRAF1) is a crucial signaling adaptor involved in multiple cellular events. However, its role in regulating osteoclastogenesis and energy metabolism remains unclear. Here, we report that TRAF1 promotes osteoclastogenesis and oxidative phosphorylation (OXPHOS).
View Article and Find Full Text PDFCorrelations between spinopelvic parameters and health-related quality of life in degenerative lumbar scoliosis patients before and after long -level fusion surgery.
BMC Musculoskelet Disord
January 2025
Department of Orthopedics, Peking University Third Hospital, No. 49. North Garden Street, Hai Dian District, Beijing, 100191, People's Republic of China.
Background: For degenerative lumbar scoliosis (DLS), prior studies mainly focused on the preoperative relationship between spinopelvic parameters and health-related quality of life (HRQoL), lacking an exhaustive evaluation of the postoperative situation. Therefore, the postoperative parameters most closely bonded with clinical outcomes has not yet been well-defined in DLS patients. The objective of this study was to comprehensively assess the correlation between radiographic parameters and HRQoL before and after surgery, and to identified the most valuable spinopelvic parameters for postoperative curative effect.
View Article and Find Full Text PDFReverse-engineering the FLT3-PI3K/AKT axis to enhance TILs function and improve prognosis in ovarian and cervical cancers.
J Ovarian Res
January 2025
Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, #128 Shenyang Road, Shanghai, 200090, People's Republic of China.
Background: Ovarian cancers (OC) and cervical cancers (CC) have poor survival rates. Tumor-infiltrating lymphocytes (TILs) play a pivotal role in prognosis, but shared immune mechanisms remain elusive.
Methods: We integrated single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) to explore immune regulation in OC and CC, focusing on the PI3K/AKT pathway and FLT3 as key modulators.
Endogenous peptide CBDP1 inhibits clear cell renal cell carcinoma progression by targeting USP5/YTHDF2/TRPM5 axis.
J Transl Med
January 2025
Medical School of Nanjing University, Nanjing, 210093, China.
Background: Clear cell renal cell carcinoma (ccRCC) has a high incidence rate and poor prognosis, and currently lacks effective therapies. Recently, peptide-based drugs have shown promise in cancer treatment. In this research, a new endogenous peptide called CBDP1 was discovered in ccRCC and its potential anti-cancer properties were examined.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!