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Protein kinase CK2 modulation of pyruvate kinase M isoforms augments the Warburg effect in cancer cells
Author(s) -
Yang Kyung Mi,
Kim Kunhong
Publication year - 2018
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.27078
Subject(s) - warburg effect , cancer cell , lactate dehydrogenase a , pkm2 , anaerobic glycolysis , glycolysis , pyruvate kinase , cell growth , kinase , biology , cancer , microbiology and biotechnology , cancer research , chemistry , biochemistry , metabolism , genetics
Protein kinase CK2 is active in cancer cells. Previously, we reported that increased CK2 activity could induce epithelial mesenchymal transition of cancer cells. CK2 also induced epithelial mesenchymal transition in colon cancer cell lines such as HT29 and SW620, and the transitioned cells (CK2α cells) became more proliferative than the controls. We assumed that CK2 could affect cancer cell growth by modulating their energy metabolism. Here, we examined the molecular effects of CK2 on the glucose metabolism of cancer cells. We found that CK2α cells consumed more glucose and produced more lactate than control cells did. An XF glycolysis stress test showed that aerobic glycolysis was augmented up to the cancer cell’s maximal glycolytic capacity in CK2α cells. Molecular analysis revealed that pyruvate kinase M1 was downregulated and pyruvate kinase M2 was nuclear localized in CK2α cells. Consequently, the expression and activity of lactate dehydrogenase A (LDHA) were upregulated. Treatment with FX11—a specific LDHA inhibitor—or clustered regularly interspaced short palindromic repeats (CRISPR)‐mediated knockout of LDHA inhibited the CK2‐driven proliferation of cancer cells. We conclude that CK2 augments the Warburg effect, resulting in increased proliferation of cancer cells.