Pyruvate Kinase M2 and Cancer: The Role of PKM2 in Promoting Tumorigenesis

Pyruvate kinase plays a pivotal role in regulating cell metabolism. The final and rate-limiting step of glycolysis is the conversion of Phosphoenolpyruvate (PEP) to Pyruvate, which is catalyzed by Pyruvate Kinase. There are four isomeric, tissue-specific forms of Pyruvate Kinase found in mammals: PK...

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Published in:Frontiers in oncology Vol. 10; p. 159
Main Authors: Zahra, Kulsoom, Dey, Tulika, Ashish, Mishra, Surendra Pratap, Pandey, Uma
Format: Journal Article
Language:English
Published: Switzerland Frontiers Media S.A 02.03.2020
Subjects:
anaerobic glycolysis
angiogenesis
cancer metabolism
chemotherapy
Oncology
pyruvate kinase M2
cancer metabolism
anaerobic glycolysis
chemotherapy
angiogenesis
pyruvate kinase M2
ISSN:2234-943X, 2234-943X
Online Access:Get full text
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Summary:Pyruvate kinase plays a pivotal role in regulating cell metabolism. The final and rate-limiting step of glycolysis is the conversion of Phosphoenolpyruvate (PEP) to Pyruvate, which is catalyzed by Pyruvate Kinase. There are four isomeric, tissue-specific forms of Pyruvate Kinase found in mammals: PKL, PKR, PKM1, and PKM2. PKM1 and PKM2 are formed bya single mRNA transcript of the PKM gene by alternative splicing. The oligomers of PKM2 exist in high activity tetramer and low activity dimer forms. The dimer PKM2 regulates the rate-limiting step of glycolysis that shifts the glucose metabolism from the normal respiratory chain to lactate production in tumor cells. Besides its role as a metabolic regulator, it also acts as protein kinase, which contributes to tumorigenesis. This review is focused on the metabolic role of pyruvate kinase M2 in normal cells vs. cancerous cells and its regulation at the transcriptional level. The review also highlights the role of PKM2 as a potential diagnostic marker and as a therapeutic target in cancer treatment.
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This article was submitted to Cancer Metabolism, a section of the journal Frontiers in Oncology
Reviewed by: Douglas Auld, Novartis Institutes for BioMedical Research, United States; Thomas N. Seyfried, Boston College, United States
Edited by: Yong Teng, Augusta University, United States
ISSN:2234-943X
2234-943X
DOI:10.3389/fonc.2020.00159