Pyruvate kinase M2 prevents apoptosis via modulating Bim stability and associates with poor outcome in hepatocellular carcinoma
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Wen Hu1,2,*, Shi-Xun Lu1,2,*, Min Li1,2, Chao Zhang1,2, Li-Li Liu1,2, Jia Fu1,2, Jie-Tian Jin1,2, Rong-Zhen Luo1,2, Chris Zhiyi Zhang1,2, Jing-Ping Yun1,2
1Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China
2Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China
*These authors have contributed equally to this work
Chris Zhiyi Zhang, e-mail: firstname.lastname@example.org
Jing-Ping Yun, e-mail: email@example.com
Keywords: PKM2, Bim, apoptosis, hepatocellular carcinoma
Received: December 26, 2014 Accepted: January 30, 2015 Published: March 02, 2015
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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