Turning on a fuel switch of cancer: hnRNP proteins regulate alternative splicing of pyruvate kinase mRNA.
Unlike normal cells, which metabolize glucose by oxidative phosphorylation for efficient energy production, tumor cells preferentially metabolize glucose by aerobic glycolysis, which produces less energy but facilitates the incorporation of more glycolytic metabolites into the biomass needed for rapid proliferation. The metabolic shift from oxidative phosphorylation to aerobic glycolysis is partly achieved by a switch in the splice isoforms of the glycolytic enzyme pyruvate kinase. Although normal cells express the pyruvate kinase M1 isoform (PKM1), tumor cells predominantly express the M2 isoform (PKM2). Switching from PKM1 to PKM2 promotes aerobic glycolysis and provides a selective advantage for tumor formation. The PKM1/M2 isoforms are generated through alternative splicing of two mutually exclusive exons. A recent study shows that the alternative splicing event is controlled by heterogeneous nuclear ribonucleoprotein (hnRNP) family members hnRNPA1, hnRNPA2, and polypyrimidine tract binding protein (PTB; also known as hnRNPI). These findings not only provide additional evidence that alternative splicing plays an important role in tumorigenesis, but also shed light on the molecular mechanism by which hnRNP proteins regulate cell proliferation in cancer.
Chen
Mo
M
Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
Zhang
Jian
J
Manley
James L
JL
D017398:Alternative Splicing; D006019:Glycolysis; D034441:Heterogeneous-Nuclear Ribonucleoproteins / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008957:Models, Genetic; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D038941:Polypyrimidine Tract-Binding Protein / Q000378:metabolism*; D011770:Pyruvate Kinase / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics
D034441:Heterogeneous-Nuclear Ribonucleoproteins; D007527:Isoenzymes; C450006:PTBP1 protein, human; D012333:RNA, Messenger; D038941:Polypyrimidine Tract-Binding Protein; D011770:Pyruvate Kinase