Pyruvate kinase M2 is a poor prognostic marker of and a therapeutic target in ovarian cancer

Tai Kuang Chao, Tien Shuo Huang, Yu Ping Liao, Rui Lan Huang, Po Hsuan Su, Hueng Yuan Shen, Hung Cheng Lai, Yu Chi Wang

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Pyruvate kinase M2 (PKM2) regulates glycolysis and oxidative phosphorylation; however, the role of PKM2 in ovarian cancer remains largely unknown. We investigated whether ovarian cancer metabolism could provide insight into the development of therapeutic strategies. We performed immunohistochemical staining for PKM2 on a tissue microarray for multivariate analysis. It revealed that patients exhibiting higher PKM2 expression were significantly associated with malignancy groups (p < 0.001) and pathogenesis models (p < 0.001), had poor progression-free survival rates (p = 0.01) as compared with patients exhibiting lower PKM2 levels, and yielded a hazard ratio of death of 2.02 (95% confidence interval: 0.70–5.85). In cell lines, PKM2 inhibitor significantly inhibited the glycolytic rate according to cellular glucose consumption (p < 0.001). We also utilized Seahorse assays to assess metabolism-related cell-specific factors and the impact of PKM2 inhibitors. Energy shifts as per Seahorse analysis showed attenuation of the extracellular acidification rate (p < 0.05) and no significant difference in oxygen-consumption rate in SKOV3 cells. Treatment with PKM2 inhibitor suppressed ovarian cancer growth and cell migration in vitro and inhibited tumor growth without significant toxicity in a xenograft study. PKM2 inhibition disturbed Warburg effects and inhibited ovarian cancer cell growth. Targeting PKM2 may constitute a promising therapy for patients with ovarian cancer, and clinical trials involving shikonin are warranted.

Original languageEnglish
Article numbere0182166
JournalPLoS One
Volume12
Issue number7
DOIs
Publication statusPublished - Jul 1 2017

Fingerprint

pyruvate kinase
Pyruvate Kinase
ovarian neoplasms
Ovarian Neoplasms
therapeutics
Syngnathidae
Smegmamorpha
Therapeutics
Metabolism
Growth
Tissue Array Analysis
metabolism
oxidative phosphorylation
Acidification
Oxidative Phosphorylation
Cell growth
glycolysis
Glycolysis
Microarrays
toxicity testing

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Chao, T. K., Huang, T. S., Liao, Y. P., Huang, R. L., Su, P. H., Shen, H. Y., ... Wang, Y. C. (2017). Pyruvate kinase M2 is a poor prognostic marker of and a therapeutic target in ovarian cancer. PLoS One, 12(7), [e0182166]. https://doi.org/10.1371/journal.pone.0182166

Pyruvate kinase M2 is a poor prognostic marker of and a therapeutic target in ovarian cancer. / Chao, Tai Kuang; Huang, Tien Shuo; Liao, Yu Ping; Huang, Rui Lan; Su, Po Hsuan; Shen, Hueng Yuan; Lai, Hung Cheng; Wang, Yu Chi.

In: PLoS One, Vol. 12, No. 7, e0182166, 01.07.2017.

Research output: Contribution to journalArticle

Chao, Tai Kuang ; Huang, Tien Shuo ; Liao, Yu Ping ; Huang, Rui Lan ; Su, Po Hsuan ; Shen, Hueng Yuan ; Lai, Hung Cheng ; Wang, Yu Chi. / Pyruvate kinase M2 is a poor prognostic marker of and a therapeutic target in ovarian cancer. In: PLoS One. 2017 ; Vol. 12, No. 7.
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