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Protein kinase CK2 modulation of pyruvate kinase M isoforms augments the Warburg effect in cancer cells.

Authors
 Kyung Mi Yang  ;  Kunhong Kim 
Citation
 JOURNAL OF CELLULAR BIOCHEMISTRY, Vol.119(10) : 8501-8510, 2018 
Journal Title
 JOURNAL OF CELLULAR BIOCHEMISTRY 
ISSN
 0730-2312 
Issue Date
2018
Keywords
Warburg effect ; aerobic glycolysis ; lactate dehydrogenase A ; protein kinase CK2 ; pyruvate kinase M1/M2
Abstract
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.
Full Text
https://onlinelibrary.wiley.com/doi/abs/10.1002/jcb.27078
DOI
10.1002/jcb.27078
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Kun Hong(김건홍) ORCID logo https://orcid.org/0000-0001-5639-6372
Yang, Kyung Mi(양경미)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/165218
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