ArticleOncogene2021
Reciprocal REGγ-mTORC1 regulation promotes glycolytic metabolism in hepatocellular carcinoma.
Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 23 citations in OpenAlex.
- Comprehensive proteomic and pathological profiling identifies PRAS40 as a novel biomarker and mediator of primary immune checkpoint blockade resistance in non-small cell lung cancer.Cancer immunology, immunotherapy : CII · 2025Article
- REGγ regulates antiviral response by activating TBK1-IFNβ signaling through degradation of PPP2CB.Cellular and molecular life sciences : CMLS · 2025Article
- PA28γ promotes the malignant progression of tumor by elevating mitochondrial function via C1QBP.eLife · 2025Article
- Thyroid hormones inhibit tumor progression and enhance the antitumor activity of lenvatinib in hepatocellular carcinoma via reprogramming glucose metabolism.Cell death discovery · 2025Article
- RABIF promotes hepatocellular carcinoma progression through regulation of mitophagy and glycolysis.Communications biology · 2024Article
- cNEK6 induces gemcitabine resistance by promoting glycolysis in pancreatic ductal adenocarcinoma via the SNRPA/PPA2c/mTORC1 axis.Cell death & disease · 2024Article
- REGγ deficiency ameliorates hepatic ischemia and reperfusion injury in a mitochondrial p66shc dependent manner in mice.Translational gastroenterology and hepatology · 2024Article
- B3galt5 deficiency attenuates hepatocellular carcinoma by suppressing mTOR/p70s6k-mediated glycolysis.Cellular and molecular life sciences : CMLS · 2022Article
- Identification of a BRAF/PA28γ/MEK1 signaling axis and its role in epithelial-mesenchymal transition in oral submucous fibrosis.Cell death & disease · 2022Article
- Regulation of Life & Death by REGγ.Cells · 2022Review
- Identification and Validation of a Novel Immune Infiltration-Based Diagnostic Score for Early Detection of Hepatocellular Carcinoma by Machine-Learning Strategies.Gastroenterology research and practice · 2022Article
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite significant progression in the study of hepatocellular carcinoma (HCC), the role of the proteasome in regulating cross talk between mTOR signaling and glycolysis in liver cancer progression is not fully understood. Here, we demonstrate that deficiency of REGγ, a proteasome activator, in mice significantly attenuates DEN-induced liver tumor formation. Ablation of REGγ increases the stability of PP2Ac (protein phosphatase 2 catalytic subunit) in vitro and in vivo, which dephosphorylates PRAS40 (AKT1 substrate 1) and stabilizes the interaction between PRAS40 and Raptor to inactive mTORC1-mediated hyper-glycolytic metabolism. In the DEN-induced animal model and clinical hepato-carcinoma samples, high levels of REGγ in HCC tumor regions contribute to reduced expression of PP2Ac, leading to accumulation of phosphorylated PRAS40 and mTORC1-mediated activation of HIF1α. Interestingly, mTORC1 enhances REGγ activity in HCC, forming a positive feedback regulatory loop. In conclusion, our study identifies REGγ-PP2Ac-PRAS40 axis as a new layer in regulating mTORC1 activity and downstream glycolytic alterations during HCC development, highlighting the REGγ-proteasome as a potential target for personalized HCC therapy.
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Registered trials
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