Nature cell biology, 2017-11, Vol.19 (11), p.1358
2017
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- Autor(en) / Beteiligte
- Titel
- PKM2 methylation by CARM1 activates aerobic glycolysis to promote tumorigenesis
- Ist Teil von
- Nature cell biology, 2017-11, Vol.19 (11), p.1358
- Ort / Verlag
- England
- Erscheinungsjahr
- 2017
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Metabolic reprogramming is a hallmark of cancer. Herein we discover that the key glycolytic enzyme pyruvate kinase M2 isoform (PKM2), but not the related isoform PKM1, is methylated by co-activator-associated arginine methyltransferase 1 (CARM1). PKM2 methylation reversibly shifts the balance of metabolism from oxidative phosphorylation to aerobic glycolysis in breast cancer cells. Oxidative phosphorylation depends on mitochondrial calcium concentration, which becomes critical for cancer cell survival when PKM2 methylation is blocked. By interacting with and suppressing the expression of inositol-1,4,5-trisphosphate receptors (InsP Rs), methylated PKM2 inhibits the influx of calcium from the endoplasmic reticulum to mitochondria. Inhibiting PKM2 methylation with a competitive peptide delivered by nanoparticles perturbs the metabolic energy balance in cancer cells, leading to a decrease in cell proliferation, migration and metastasis. Collectively, the CARM1-PKM2 axis serves as a metabolic reprogramming mechanism in tumorigenesis, and inhibiting PKM2 methylation generates metabolic vulnerability to InsP R-dependent mitochondrial functions.
- Sprache
- Englisch
- Identifikatoren
- eISSN: 1476-4679DOI: 10.1038/ncb3630Titel-ID: cdi_pubmed_primary_29058718
- Format
- –
- Schlagworte
- Animals, Calcium - metabolism, Carcinogenesis - metabolism, Carcinogenesis - pathology, CARD Signaling Adaptor Proteins - metabolism, Carrier Proteins - metabolism, Cell Line, Cell Line, Tumor, Cell Movement - physiology, Cell Proliferation - physiology, Endoplasmic Reticulum - metabolism, Female, Glycolysis - physiology, Guanylate Cyclase - metabolism, HEK293 Cells, Humans, Inositol 1,4,5-Trisphosphate Receptors - metabolism, MCF-7 Cells, Membrane Proteins - metabolism, Methylation, Mice, Mice, Inbred BALB C, Mice, Nude, Mitochondria - metabolism, Neoplasm Metastasis - pathology, Oxidative Phosphorylation, Thyroid Hormone-Binding Proteins, Thyroid Hormones - metabolism