Tumor Pyruvate Kinase M2: A Promising Molecular Target of Gastrointestinal Cancer

Overview

Journal Chin J Cancer Res

Specialty Oncology

Date 2019 Feb 1

PMID 30700935

Citations 4

Authors

Chen Guo

Guan Li

Jianing Hou

Xingming Deng

Sheng Ao

Zhuofei Li

Guoqing Lyu

Affiliations

Soon will be listed here.

Abstract

Gastrointestinal (GI) cancer is one of the most common causes of cancer-related deaths worldwide. Tumor markers are valuable in detecting post-surgical recurrence or in monitoring response to chemotherapy. Pyruvate kinase isoform M2 (PKM2), a glycolytic enzyme catalyzing conversion of phosphoenolpyruvate (PEP) to pyruvate, confers a growth advantage to the tumor cells and enables them to adapt to the tumor microenvironment. In this review, we have summarized current research on the expression and regulation of PKM2 in tumor cells, and its potential role in GI carcinogenesis and progression. Furthermore, we have also discussed the potential of PKM2 as a diagnostic and screening marker, and a therapeutic target in GI cancer.

Citing Articles

Extracts as Novel PKM2 Inhibitors for Treatment of Triple Negative Breast Cancer.

Rasul A, Riaz A, Wei W, Sarfraz I, Hassan M, Li J Biomed Res Int. 2021; 2021:5514669.

PMID: 34136566 PMC: 8175167. DOI: 10.1155/2021/5514669.

A Novel Glycolysis-Related Four-mRNA Signature for Predicting the Survival of Patients With Breast Cancer.

Zhang X, Wang J, Zhuang J, Liu C, Gao C, Li H Front Genet. 2021; 12:606937.

PMID: 33584825 PMC: 7876610. DOI: 10.3389/fgene.2021.606937.

Protein kinase function of pyruvate kinase M2 and cancer.

Chen X, Chen S, Yu D Cancer Cell Int. 2020; 20(1):523.

PMID: 33292198 PMC: 7597019. DOI: 10.1186/s12935-020-01612-1.

Prognostic implications of epidermal growth factor receptor variant III expression and nuclear translocation in Chinese human gliomas.

Yang K, Ren X, Tao L, Wang P, Jiang H, Shen L Chin J Cancer Res. 2019; 31(1):188-202.

PMID: 30996577 PMC: 6433583. DOI: 10.21147/j.issn.1000-9604.2019.01.14.

References

McLaughlin R, OHanlon D, Kerin M, Kenny P, Grimes H, Given H . Are elevated levels of the tumour marker CA19-9 of any clinical significance?--an evaluation. Ir J Med Sci. 1999; 168(2):124-6. DOI: 10.1007/BF02946481. View

Pokorny R, Hunt L, Galandiuk S . What's new with tumor markers for colorectal cancer?. Dig Surg. 2000; 17(3):209-15. DOI: 10.1159/000018853. View

Mann D, Edwards R, Ho S, Lau W, Glazer G . Elevated tumour marker CA19-9: clinical interpretation and influence of obstructive jaundice. Eur J Surg Oncol. 2000; 26(5):474-9. DOI: 10.1053/ejso.1999.0925. View

Sears R, Nuckolls F, Haura E, Taya Y, Tamai K, Nevins J . Multiple Ras-dependent phosphorylation pathways regulate Myc protein stability. Genes Dev. 2000; 14(19):2501-14. PMC: 316970. DOI: 10.1101/gad.836800. View

Mathupala S, Rempel A, Pedersen P . Glucose catabolism in cancer cells: identification and characterization of a marked activation response of the type II hexokinase gene to hypoxic conditions. J Biol Chem. 2001; 276(46):43407-12. DOI: 10.1074/jbc.M108181200. View

Gambhir S . Molecular imaging of cancer with positron emission tomography. Nat Rev Cancer. 2002; 2(9):683-93. DOI: 10.1038/nrc882. View

Longley D, Harkin D, Johnston P . 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003; 3(5):330-8. DOI: 10.1038/nrc1074. View

Warburg O . On the origin of cancer cells. Science. 1956; 123(3191):309-14. DOI: 10.1126/science.123.3191.309. View

Dombrauckas J, Santarsiero B, Mesecar A . Structural basis for tumor pyruvate kinase M2 allosteric regulation and catalysis. Biochemistry. 2005; 44(27):9417-29. DOI: 10.1021/bi0474923. View

10.

Christofk H, Vander Heiden M, Wu N, Asara J, Cantley L . Pyruvate kinase M2 is a phosphotyrosine-binding protein. Nature. 2008; 452(7184):181-6. DOI: 10.1038/nature06667. View

11.

Hsu P, Sabatini D . Cancer cell metabolism: Warburg and beyond. Cell. 2008; 134(5):703-7. DOI: 10.1016/j.cell.2008.08.021. View

12.

Vander Heiden M, Cantley L, Thompson C . Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science. 2009; 324(5930):1029-33. PMC: 2849637. DOI: 10.1126/science.1160809. View

13.

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

14.

David C, Chen M, Assanah M, Canoll P, Manley J . HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer. Nature. 2009; 463(7279):364-8. PMC: 2950088. DOI: 10.1038/nature08697. View

15.

Mazurek S . Pyruvate kinase type M2: a key regulator of the metabolic budget system in tumor cells. Int J Biochem Cell Biol. 2010; 43(7):969-80. DOI: 10.1016/j.biocel.2010.02.005. View

16.

Jemal A, Siegel R, Xu J, Ward E . Cancer statistics, 2010. CA Cancer J Clin. 2010; 60(5):277-300. DOI: 10.3322/caac.20073. View

17.

Harada K, SAHEKI S, Wada K, Tanaka T . Purification of four pyruvate kinase isozymes of rats by affinity elution chromatography. Biochim Biophys Acta. 1978; 524(2):327-39. DOI: 10.1016/0005-2744(78)90169-9. View

18.

Hanahan D, Weinberg R . Hallmarks of cancer: the next generation. Cell. 2011; 144(5):646-74. DOI: 10.1016/j.cell.2011.02.013. View

19.

Li R, Liu J, Xue H, Huang G . Diagnostic value of fecal tumor M2-pyruvate kinase for CRC screening: a systematic review and meta-analysis. Int J Cancer. 2012; 131(8):1837-45. DOI: 10.1002/ijc.27442. View

20.

Chaneton B, Gottlieb E . Rocking cell metabolism: revised functions of the key glycolytic regulator PKM2 in cancer. Trends Biochem Sci. 2012; 37(8):309-16. DOI: 10.1016/j.tibs.2012.04.003. View