title: Pyruvate kinase M2 prevents apoptosis via modulating Bim stability and associates with poor outcome in hepatocellular carcinoma.
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.
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.|Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors: Wen
authors: W
authors: Hu
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.|Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors: Shi-Xun
authors: SX
authors: Lu
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.|Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors: Min
authors: M
authors: Li
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.|Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors: Chao
authors: C
authors: Zhang
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.|Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors: Li-Li
authors: LL
authors: Liu
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.|Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors: Jia
authors: J
authors: Fu
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.|Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors: Jie-Tian
authors: JT
authors: Jin
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.|Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors: Rong-Zhen
authors: RZ
authors: Luo
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.|Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors: Chris Zhiyi
authors: CZ
authors: Zhang
authors: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China.|Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
authors: Jing-Ping
authors: JP
authors: Yun
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D000072224:Bcl-2-Like Protein 11; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018572:Disease-Free Survival; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008819:Mice, Nude; D015999:Multivariate Analysis; D055550:Protein Stability; D059748:Proteolysis; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D000067492:RNAi Therapeutics; D015398:Signal Transduction; D013963:Thyroid Hormones / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D023041:Xenograft Model Antitumor Assays; D000097810:Thyroid Hormone-Binding Proteins
chemical_list: D051017:Apoptosis Regulatory Proteins; D000072224:Bcl-2-Like Protein 11; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D008565:Membrane Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D013963:Thyroid Hormones; D000097810:Thyroid Hormone-Binding Proteins; C000606775:BCL2L11 protein, human; C000606776:Bcl2l11 protein, mouse
keywords: Bim; PKM2; apoptosis; hepatocellular carcinoma