» Articles » PMID: 23476652

PKM2, a Central Point of Regulation in Cancer Metabolism

Overview
Journal Int J Cell Biol
Publisher Wiley
Specialty Cell Biology
Date 2013 Mar 12
PMID 23476652
Citations 114
Authors
Affiliations
Soon will be listed here.
Abstract

Aerobic glycolysis is the dominant metabolic pathway utilized by cancer cells, owing to its ability to divert glucose metabolites from ATP production towards the synthesis of cellular building blocks (nucleotides, amino acids, and lipids) to meet the demands of proliferation. The M2 isoform of pyruvate kinase (PKM2) catalyzes the final and also a rate-limiting reaction in the glycolytic pathway. In the PK family, PKM2 is subjected to a complex regulation by both oncogenes and tumour suppressors, which allows for a fine-tone regulation of PKM2 activity. The less active form of PKM2 drives glucose through the route of aerobic glycolysis, while active PKM2 directs glucose towards oxidative metabolism. Additionally, PKM2 possesses protein tyrosine kinase activity and plays a role in modulating gene expression and thereby contributing to tumorigenesis. We will discuss our current understanding of PKM2's regulation and its many contributions to tumorigenesis.

Citing Articles

The Role of the Dysregulation of circRNAs Expression in Glioblastoma Multiforme.

Wang Y, Yu Y, Yu J, Wang C, Wang Y, Fu R J Mol Neurosci. 2025; 75(1):9.

PMID: 39841303 DOI: 10.1007/s12031-024-02285-5.


SRT3025-loaded cell membrane hybrid liposomes (3025@ML) enhanced anti-tumor activity of Oxaliplatin via inhibiting pyruvate kinase M2 and fatty acid synthase.

Wang X, Li S, Li Z, Lin Z, Wang Z Lipids Health Dis. 2025; 24(1):14.

PMID: 39825408 PMC: 11740399. DOI: 10.1186/s12944-025-02431-x.


Effective-Component Compatibility of Bufei Yishen Formula III Suppresses Mitochondrial Oxidative Damage in COPD: Via Pkm2/Nrf2 Pathway.

Liu Y, Zhang L, Zhao J, Lu R, Shao X, Xu K Int J Chron Obstruct Pulmon Dis. 2024; 19:1905-1920.

PMID: 39206144 PMC: 11352541. DOI: 10.2147/COPD.S468825.


Chrysophanol inhibits of colorectal cancer cell motility and energy metabolism by targeting the KITENIN/ErbB4 oncogenic complex.

Varli M, Kim E, Oh S, Pulat S, Zhou R, Gamage C Cancer Cell Int. 2024; 24(1):253.

PMID: 39030594 PMC: 11264950. DOI: 10.1186/s12935-024-03434-x.


The role of PKM2 in cancer progression and its structural and biological basis.

Wu B, Liang Z, Lan H, Teng X, Wang C J Physiol Biochem. 2024; 80(2):261-275.

PMID: 38329688 DOI: 10.1007/s13105-024-01007-0.


References
1.
Hitosugi T, Kang S, Vander Heiden M, Chung T, Elf S, Lythgoe K . Tyrosine phosphorylation inhibits PKM2 to promote the Warburg effect and tumor growth. Sci Signal. 2009; 2(97):ra73. PMC: 2812789. DOI: 10.1126/scisignal.2000431. View

2.
Wang S, Bourguignon L . Role of hyaluronan-mediated CD44 signaling in head and neck squamous cell carcinoma progression and chemoresistance. Am J Pathol. 2011; 178(3):956-63. PMC: 3069910. DOI: 10.1016/j.ajpath.2010.11.077. View

3.
Ye J, Mancuso A, Tong X, Ward P, Fan J, Rabinowitz J . Pyruvate kinase M2 promotes de novo serine synthesis to sustain mTORC1 activity and cell proliferation. Proc Natl Acad Sci U S A. 2012; 109(18):6904-9. PMC: 3345000. DOI: 10.1073/pnas.1204176109. View

4.
Wechsel H, Petri E, Bichler K, Feil G . Marker for renal cell carcinoma (RCC): the dimeric form of pyruvate kinase type M2 (Tu M2-PK). Anticancer Res. 1999; 19(4A):2583-90. View

5.
Kwon O, Kang T, Kim J, Kim M, Noh S, Song K . Pyruvate kinase M2 promotes the growth of gastric cancer cells via regulation of Bcl-xL expression at transcriptional level. Biochem Biophys Res Commun. 2012; 423(1):38-44. DOI: 10.1016/j.bbrc.2012.05.063. View