ArticleCell death and differentiation2020
Epigenetic regulation of the Warburg effect by H2B monoubiquitination.
Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 54 citations in OpenAlex.
- NSD2 inhibits the expression of PD-L1 via oxidative phosphorylation to control immune surveillance in hepatocellular carcinoma.Cell death & disease · 2026Article
- Metabolic enzyme-associated protein-protein interactions (mPPIs) in cancer: potential vulnerability for cancer treatment?Acta pharmacologica Sinica · 2025Review
- Mitochondrial metabolism and cancer therapeutic innovation.Signal transduction and targeted therapy · 2025Review
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- Moonlighting functions of glucose metabolic enzymes and metabolites in cancer.Nature reviews. Cancer · 2025Review
- Exosome-Mediated Chemoresistance in Cancers: Mechanisms, Therapeutic Implications, and Future Directions.Biomolecules · 2025Review
- AC129507.1 is a ferroptosis-related target identified by a novel mitochondria-related lncRNA signature that is involved in the tumor immune microenvironment in gastric cancer.Journal of translational medicine · 2025Article
- Mechanisms and therapeutic perspectives of mitochondrial dysfunction of macrophages in periodontitis.Frontiers in cellular and infection microbiology · 2025Review
- PKM2-driven metabolic reprogramming in digestive system tumors: mechanisms, therapeutic advances, and clinical challenges.Frontiers in immunology · 2025Review
- Advances of E3 ligases in lung cancer.Biochemistry and biophysics reports · 2024Review
- Metformin Increases the Response of Cholangiocarcinoma Cells to Gemcitabine by Suppressing Pyruvate Kinase M2 to Activate Mitochondrial Apoptosis.Digestive diseases and sciences · 2024Article
- Article
- Regulative Roles of Metabolic Plasticity Caused by Mitochondrial Oxidative Phosphorylation and Glycolysis on the Initiation and Progression of Tumorigenesis.International journal of molecular sciences · 2023Review
- GTPBP4 promotes hepatocellular carcinoma progression and metastasis via the PKM2 dependent glucose metabolism.Redox biology · 2022Article
- UPP1 Promotes Lung Adenocarcinoma Progression through Epigenetic Regulation of Glycolysis.Aging and disease · 2022Article
- Long non-coding RNAs affecting cell metabolism in cancer.Biology direct · 2022Review
- Gankyrin modulated non-small cell lung cancer progression via glycolysis metabolism in a YAP1-dependent manner.Cell death discovery · 2022Article
- Monoubiquitination in Homeostasis and Cancer.International journal of molecular sciences · 2022Review
- USP47 stabilizes BACH1 to promote the Warburg effect and non-small cell lung cancer development via stimulating Hk2 and Gapdh transcription.American journal of cancer research · 2022Article
- A nonautophagic role of ATG5 in regulating cell growth by targeting c-Myc for proteasome-mediated degradation.iScience · 2021Article
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Authors and funding
12 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer cells reprogram their energy metabolic system from the mitochondrial oxidative phosphorylation (OXPHOS) pathway to a glucose-dependent aerobic glycolysis pathway. This metabolic reprogramming phenomenon is known as the Warburg effect, a significant hallmark of cancer. However, the detailed mechanisms underlying this event or triggering this reprogramming remain largely unclear. Here, we found that histone H2B monoubiquitination (H2Bub1) negatively regulates the Warburg effect and tumorigenesis in human lung cancer cells (H1299 and A549 cell lines) likely through controlling the expression of multiple mitochondrial respiratory genes, which are essential for OXPHOS. Moreover, our work also suggested that pyruvate kinase M2 (PKM2), the rate-limiting enzyme of glycolysis, can directly interact with H2B in vivo and in vitro and negatively regulate the level of H2Bub1. The inhibition of cell proliferation and nude mice xenograft of human lung cancer cells induced by PKM2 knockdown can be partially rescued through lowering H2Bub1 levels, which indicates that the oncogenic function of PKM2 is achieved, at least partially, through the control of H2Bub1. Furthermore, PKM2 and H2Bub1 levels are negatively correlated in cancer specimens. Therefore, these findings not only provide a novel mechanism triggering the Warburg effect that is mediated through an epigenetic pathway (H2Bub1) but also reveal a novel metabolic regulator (PKM2) for the epigenetic mark H2Bub1. Thus, the PKM2-H2Bub1 axis may become a promising cancer therapeutic target.
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