Pyruvate kinase M2 prevents apoptosis via modulating Bim stability and associates with poor outcome in hepatocellular carcinoma

Oncotarget
Wen HuJing-Ping Yun

Abstract

Pyruvate kinase M2 (PKM2) contributes to the Warburg effect, a hallmark of cancer. We showed that PKM2 levels were correlated with overall survival (hazard ration = 1.675, 95% confidence interval: 1.389-2.019, P < 0.001) and disease-free survival (hazard ration = 1.573, 95% confidence interval: 1.214-2.038, P < 0.001) in a cohort of 490 patients with HCC. The correlations were further validated in an independent cohort of 148 HCC patients. Multivariate analyses revealed that PKM2 was an independent indicator of poor outcome in HCC. The knockdown of PKM2 in HCC cells inhibited cell proliferation and induced apoptosis in vitro and in vivo. Bim siRNA markedly abolished the PKM2-depletion-induced apoptosis. PKM2 depletion decreased the degradation of Bim. In clinical samples, PKM2 expression was reversely correlated with Bim expression. Combination of PKM2 and Bim levels had the best prognostic significance. We suggest that PKM2 serves as a promising biomarker for poor prognosis of patients with HCC and its knockdown induces HCC apoptosis by stabilizing Bim.

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Citations

Oct 27, 2015·Cellular and Molecular Life Sciences : CMLS·Zhaoyong Li, Huafeng Zhang
Jul 28, 2019·Cellular and Molecular Life Sciences : CMLS·Daniela FerreiraRaquel Chaves
Sep 26, 2015·Oncotarget·Ronit Vogt SionovZvi Granot
Jun 29, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Feihu JiTingmei Chen
May 12, 2018·Current Cancer Drug Targets·A P AlvesC J Maia
Mar 3, 2019·Journal of Cancer Research and Clinical Oncology·Min YuZhixiang Jian
Aug 12, 2019·Free Radical Biology & Medicine·Mohammed AlquraishiAhmed Bettaieb
Dec 10, 2020·Analytical Cellular Pathology (Amsterdam)·Hui XiaoZhenzhong Liu
Jan 29, 2021·International Journal of Molecular Sciences·Dexter L PuckettAhmed Bettaieb
Nov 3, 2021·Journal of Medicinal Chemistry·Sahil AroraRaj Kumar

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Methods Mentioned

BETA
FACS
flow cytometry
X-ray
PCR
transfection
xenograft

Software Mentioned

Olmpus
SDS
Image J
SPSS16

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