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丙酮酸激酶M2通过募集髓源性抑制细胞促进转移,并提示肝细胞癌预后不良。

PKM2 promotes metastasis by recruiting myeloid-derived suppressor cells and indicates poor prognosis for hepatocellular carcinoma.

作者信息

Liu Wei-Ren, Tian Meng-Xin, Yang Liu-Xiao, Lin Yu-Li, Jin Lei, Ding Zhen-Bin, Shen Ying-Hao, Peng Yuan-Fei, Gao Dong-Mei, Zhou Jian, Qiu Shuang-Jian, Dai Zhi, He Rui, Fan Jia, Shi Ying-Hong

机构信息

Department 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.

Department of Immunology, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai, People's Republic of China.

出版信息

Oncotarget. 2015 Jan 20;6(2):846-61. doi: 10.18632/oncotarget.2749.

Abstract

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.

摘要

丙酮酸激酶M2(PKM2)是丙酮酸激酶家族的成员。最近的研究确定了PKM2的“非代谢”功能。然而,PKM2在肝癌中的作用仍不清楚。为了研究PKM2在肿瘤生长、侵袭及肝细胞癌(HCC)预后中的作用,采用qRT-PCR、蛋白质免疫印迹和免疫荧光分析检测了HCC细胞系和组织中PKM2的表达。在体外实验中,使用短发夹RNA慢病毒载体敲低PKM2,并分析肿瘤细胞行为、下游信号通路和趋化因子。为了分析体内肿瘤生长情况,检测了裸鼠肿瘤内和肿瘤周围的淋巴细胞浸润情况。通过免疫组织化学分析了包括721例HCC患者的两个队列中PKM2的预后价值。总之,我们从细胞系、致瘤性研究和原发性HCC样本中获得的数据表明PKM2在肿瘤中具有致癌作用。此外,PKM2可能作为HCC患者根治性切除后的一种新的预后指标,针对PKM2的靶向治疗可能是HCC的一种有效治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d9d/4359260/2c9968ca1582/oncotarget-06-846-g001.jpg

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