PKM2 promotes metastasis by recruiting myeloid-derived suppressor cells and indicates poor prognosis for hepatocellular carcinoma
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Wei-Ren Liu1,*, Meng-Xin Tian1,*, Liu-Xiao Yang1,*, Yu-Li Lin2, Lei Jin1, Zhen-Bin Ding1, Ying-Hao Shen1, Yuan-Fei Peng1, Dong-Mei Gao1, Jian Zhou1,3, Shuang-Jian Qiu1, Zhi Dai1, Rui He2, Jia Fan1,3, Ying-Hong Shi1
1Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University; Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, People's Republic of China
2Department of Immunology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China
3Institutes of Biomedical Sciences, Fudan University, Shanghai, People's Republic of China
* These authors have contributed equally to this work
Ying-Hong Shi, e-mail: firstname.lastname@example.org
Keywords: PKM2, Myeloid-derived Suppressor Cells, Prognosis, Hepatocellular Carcinoma, Metastasis
Received: July 27, 2014 Accepted: November 11, 2014 Published: December 02, 2014
Pyruvate kinase M2 (PKM2) is a member of the pyruvate kinase family. Recent work has defined the “non-metabolic” functions of PKM2. However, the role of PKM2 in HCC remains unclear. To investigate the role of PKM2 in tumor growth, invasion and the prognosis of hepatocellular carcinoma (HCC), PKM2 expression was measured in HCC cell lines and tissues using qRT-PCR, western blot, and immunofluorescence assays. In in vitro experiments, PKM2 was knocked down using a short hairpin RNA lentivirus vector, and tumor cell behavior and the downstream signaling pathways and chemokine were analyzed. For the analysis of in vivo tumor growth, intratumoral and peritumoral lymphocyte infiltration were examined in nude mice. The prognostic value of PKM2 was analyzed by immunohistochemistry in two cohorts including 721 HCC patients. Together, our data obtained from cell lines, tumorigenicity studies, and primary HCC samples illustrate an oncogenic role for PKM2 in tumors. Moreover, PKM2 may serve as a novel prognostic indicator for HCC patients after curative resection, targeted therapy aimed at PKM2 may represent an effective treatment approach for HCC.
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