title: Pyruvate kinase M2 affects liver cancer cell behavior through up-regulation of HIF-1α and Bcl-xL in culture.
abstract: Cancer cells consume large amounts of glucose to produce lactate, even in the presence of ample oxygen. This phenomenon is known as the Warburg effect. The pyruvate kinase promotes aerobic glycolysis, and the pyruvate kinase M2 isoform (PKM2) is highly expressed in many cancer cells. Although the Warburg effect is a hallmark of cancer, the mechanism by which PKM2 contributes to the Warburg effect, and its role in tumor growth remain to be defined. We proposed that PKM2 activates transcription of hypoxia inducible factor-1α (HIF-1α) by phosphorylating STAT3 (signal transducer and activator of transcription 3) at Y705 (tyrosine 705) as a plausible mechanism for liver cancer cell proliferation. In the current study, we observed that PKM2 was over-expressed in hepatocellular carcinoma (HCC) tissues compared to adjacent normal tissues. The experiments further indicate that nuclear PKM2 is an active protein kinase in cultured cells. Knockdown of PKM2 affected the levels of HIF-1α and Bcl-xL (B-cell lymphoma-extra large), suggesting that PKM2 plays an important role in promoting cell proliferation. In conclusion, the current findings demonstrate that PKM2 is an active protein kinase, and promotes liver cancer cell proliferation by up-regulating HIF-1α and Bcl-xL expression.
authors: General Surgery Department, Lianyungang First People's Hospital, Lianyungang, Jiangsu Province, China.
authors: Tianfu
authors: T
authors: Dong
authors: Department of Infectious Diseases, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors: Youde
authors: Y
authors: Yan
authors: Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors: Hao
authors: H
authors: Chai
authors: Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors: Shenglin
authors: S
authors: Chen
authors: Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors: Xinkui
authors: X
authors: Xiong
authors: Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
authors: Daoyi
authors: D
authors: Sun
authors: Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Nanjing, Jiangsu Province, China.
authors: Yue
authors: Y
authors: Yu
authors: Key Laboratory of Living Donor Liver Transplantation, Ministry of Public Health, Nanjing, Jiangsu Province, China.
authors: Lei
authors: L
authors: Deng
authors: Liver Transplantation Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China. Electronic address: docchengfeng@njmu.edu.cn.
authors: Feng
authors: F
authors: Cheng
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D008113:Liver Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011770:Pyruvate Kinase / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D051996:Transcription Factor RelA / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D055815:Young Adult; D051020:bcl-X Protein / Q000235:genetics* / Q000378:metabolism
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D050796:STAT3 Transcription Factor; D051996:Transcription Factor RelA; D051020:bcl-X Protein; D019000:Phosphotyrosine; D011770:Pyruvate Kinase
keywords: Hypoxia inducible factor-1α; Pyruvate kinase M2; Warburg effect