Pyruvate kinase M2: Multiple faces for conferring benefits on cancer cells

Mayumi Tamada, Makoto Suematsu, Hideyuki Saya

Research output: Contribution to journalArticle

131 Citations (Scopus)

Abstract

The M2 splice isoform of pyruvate kinase (PKM2), an enzyme that catalyzes the later step of glycolysis, is a key regulator of aerobic glycolysis (known as the Warburg effect) in cancer cells. Expression and low enzymatic activity of PKM2 confer on cancer cells the glycolytic phenotype, which promotes rapid energy production and flow of glycolytic intermediates into collateral pathways to synthesize nucleic acids, amino acids, and lipids without the accumulation of reactive oxygen species.PKM2 enzymatic activity has also been shown to be negatively regulated by the interaction with CD44 adhesion molecule, which is a cell surface marker for cancer stem cells. In addition to the glycolytic functions, nonglycolytic functions of PKM2 in cancer cells are of particular interest. PKM2 is induced translocation into the nucleus, where it activates transcription of various genes by interacting with and phosphorylating specific nuclear proteins, endowing cancer cells with a survival and growth advantage. Therefore, inhibitors and activators of PKM2 are well underway to evaluate their anticancer effects and suitability for use as novel therapeutic strategies.

Original languageEnglish
Pages (from-to)5554-5561
Number of pages8
JournalClinical Cancer Research
Volume18
Issue number20
DOIs
Publication statusPublished - 2012 Oct 15

Fingerprint

Pyruvate Kinase
Glycolysis
Neoplasms
Neoplastic Stem Cells
Nuclear Proteins
Nucleic Acids
Reactive Oxygen Species
Protein Isoforms
Phenotype
Lipids
Amino Acids
Enzymes
Growth
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Pyruvate kinase M2 : Multiple faces for conferring benefits on cancer cells. / Tamada, Mayumi; Suematsu, Makoto; Saya, Hideyuki.

In: Clinical Cancer Research, Vol. 18, No. 20, 15.10.2012, p. 5554-5561.

Research output: Contribution to journalArticle

Tamada, Mayumi ; Suematsu, Makoto ; Saya, Hideyuki. / Pyruvate kinase M2 : Multiple faces for conferring benefits on cancer cells. In: Clinical Cancer Research. 2012 ; Vol. 18, No. 20. pp. 5554-5561.
@article{3462791751dd40c9abea8ef8ca6cd5ea,
title = "Pyruvate kinase M2: Multiple faces for conferring benefits on cancer cells",
abstract = "The M2 splice isoform of pyruvate kinase (PKM2), an enzyme that catalyzes the later step of glycolysis, is a key regulator of aerobic glycolysis (known as the Warburg effect) in cancer cells. Expression and low enzymatic activity of PKM2 confer on cancer cells the glycolytic phenotype, which promotes rapid energy production and flow of glycolytic intermediates into collateral pathways to synthesize nucleic acids, amino acids, and lipids without the accumulation of reactive oxygen species.PKM2 enzymatic activity has also been shown to be negatively regulated by the interaction with CD44 adhesion molecule, which is a cell surface marker for cancer stem cells. In addition to the glycolytic functions, nonglycolytic functions of PKM2 in cancer cells are of particular interest. PKM2 is induced translocation into the nucleus, where it activates transcription of various genes by interacting with and phosphorylating specific nuclear proteins, endowing cancer cells with a survival and growth advantage. Therefore, inhibitors and activators of PKM2 are well underway to evaluate their anticancer effects and suitability for use as novel therapeutic strategies.",
author = "Mayumi Tamada and Makoto Suematsu and Hideyuki Saya",
year = "2012",
month = "10",
day = "15",
doi = "10.1158/1078-0432.CCR-12-0859",
language = "English",
volume = "18",
pages = "5554--5561",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "20",

}

TY - JOUR

T1 - Pyruvate kinase M2

T2 - Multiple faces for conferring benefits on cancer cells

AU - Tamada, Mayumi

AU - Suematsu, Makoto

AU - Saya, Hideyuki

PY - 2012/10/15

Y1 - 2012/10/15

N2 - The M2 splice isoform of pyruvate kinase (PKM2), an enzyme that catalyzes the later step of glycolysis, is a key regulator of aerobic glycolysis (known as the Warburg effect) in cancer cells. Expression and low enzymatic activity of PKM2 confer on cancer cells the glycolytic phenotype, which promotes rapid energy production and flow of glycolytic intermediates into collateral pathways to synthesize nucleic acids, amino acids, and lipids without the accumulation of reactive oxygen species.PKM2 enzymatic activity has also been shown to be negatively regulated by the interaction with CD44 adhesion molecule, which is a cell surface marker for cancer stem cells. In addition to the glycolytic functions, nonglycolytic functions of PKM2 in cancer cells are of particular interest. PKM2 is induced translocation into the nucleus, where it activates transcription of various genes by interacting with and phosphorylating specific nuclear proteins, endowing cancer cells with a survival and growth advantage. Therefore, inhibitors and activators of PKM2 are well underway to evaluate their anticancer effects and suitability for use as novel therapeutic strategies.

AB - The M2 splice isoform of pyruvate kinase (PKM2), an enzyme that catalyzes the later step of glycolysis, is a key regulator of aerobic glycolysis (known as the Warburg effect) in cancer cells. Expression and low enzymatic activity of PKM2 confer on cancer cells the glycolytic phenotype, which promotes rapid energy production and flow of glycolytic intermediates into collateral pathways to synthesize nucleic acids, amino acids, and lipids without the accumulation of reactive oxygen species.PKM2 enzymatic activity has also been shown to be negatively regulated by the interaction with CD44 adhesion molecule, which is a cell surface marker for cancer stem cells. In addition to the glycolytic functions, nonglycolytic functions of PKM2 in cancer cells are of particular interest. PKM2 is induced translocation into the nucleus, where it activates transcription of various genes by interacting with and phosphorylating specific nuclear proteins, endowing cancer cells with a survival and growth advantage. Therefore, inhibitors and activators of PKM2 are well underway to evaluate their anticancer effects and suitability for use as novel therapeutic strategies.

UR - http://www.scopus.com/inward/record.url?scp=84867559423&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84867559423&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-12-0859

DO - 10.1158/1078-0432.CCR-12-0859

M3 - Article

C2 - 23071357

AN - SCOPUS:84867559423

VL - 18

SP - 5554

EP - 5561

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 20

ER -