TY - JOUR
T1 - Emerging roles of PKM2 in cell metabolism and cancer progression
AU - Luo, Weibo
AU - Semenza, Gregg L.
N1 - Funding Information:
Work in the authors’ laboratory was supported by the National Institutes of Health, American Cancer Society, and an International Cooperative Research Project award (ERATO-ICORP Gas Biology Project) from the Japan Science and Technology Agency. W.L. was supported by a fellowship from the Fowler Foundation for Advanced Research in the Medical Sciences. G.L.S. is the C. Michael Armstrong Professor at Johns Hopkins University School of Medicine and an American Cancer Society Research Professor.
PY - 2012/11
Y1 - 2012/11
N2 - Increased conversion of glucose to lactate is a key feature of many cancer cells that promotes rapid growth. Pyruvate kinase M2 (PKM2) expression is increased and facilitates lactate production in cancer cells. Modulation of PKM2 catalytic activity also regulates the synthesis of DNA and lipids that are required for cell proliferation, and of NADPH that is required for redox homeostasis. In addition to its role as a pyruvate kinase, PKM2 also functions as a protein kinase and as a transcriptional coactivator. These biochemical activities are controlled by allosteric regulators and post-translational modifications of PKM2 that include acetylation, oxidation, phosphorylation, prolyl hydroxylation, and sumoylation. Given its pleiotropic effects on cancer biology, PKM2 represents an attractive target for cancer therapy.
AB - Increased conversion of glucose to lactate is a key feature of many cancer cells that promotes rapid growth. Pyruvate kinase M2 (PKM2) expression is increased and facilitates lactate production in cancer cells. Modulation of PKM2 catalytic activity also regulates the synthesis of DNA and lipids that are required for cell proliferation, and of NADPH that is required for redox homeostasis. In addition to its role as a pyruvate kinase, PKM2 also functions as a protein kinase and as a transcriptional coactivator. These biochemical activities are controlled by allosteric regulators and post-translational modifications of PKM2 that include acetylation, oxidation, phosphorylation, prolyl hydroxylation, and sumoylation. Given its pleiotropic effects on cancer biology, PKM2 represents an attractive target for cancer therapy.
UR - http://www.scopus.com/inward/record.url?scp=84867140008&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84867140008&partnerID=8YFLogxK
U2 - 10.1016/j.tem.2012.06.010
DO - 10.1016/j.tem.2012.06.010
M3 - Review article
C2 - 22824010
AN - SCOPUS:84867140008
SN - 1043-2760
VL - 23
SP - 560
EP - 566
JO - Trends in Endocrinology and Metabolism
JF - Trends in Endocrinology and Metabolism
IS - 11
ER -