2017年2月6日，国际学术权威刊物自然出版集团旗下子刊、肿瘤学重要学术期刊《Oncogene》杂志在线发表了华中科技大学基础医学院黄波教授科研团队关于肿瘤干细胞代谢的研究成果。博士生骆顺群、李勇为本文并列第一作者，黄波教授为论文通讯作者。

肿瘤代谢研究是肿瘤的热点问题。目前肿瘤研究主要集中到肿瘤群体层面，考虑到肿瘤的层次性和异质性，缺少对肿瘤干细胞的代谢研究。在题为《下调表达线粒体型磷酸烯醇式丙酮酸羧激酶重塑黑色素瘤再生细胞的三羧酸循环》(Downregulation of PCK2 remodels tricarboxylic acid cycle in tumor-repopulating cells of melanoma)的文章中，黄波团队以前期研发的三维纤维蛋白软胶筛选和扩增的肿瘤再生细胞(Nature Materials. 2012 Jul 1; 11(8): 734–741.)为干细胞研究模型，研究肿瘤代谢途径对肿瘤再生细胞的生长及自我更新的影响。通过比较肿瘤再生细胞与分化的肿瘤细胞之间不同的代谢特性，研究发现黑色素瘤再生细胞线粒体型磷酸烯醇式丙酮酸羧激酶(PCK2)的表达下调，并证实肿瘤再生细胞下调表达PCK2调节三羧酸循环(TCA cycle)，其通过协调糖酵解、三羧酸循环和氧化磷酸化三者的关系，促进肿瘤再生细胞的生长，从而维持细胞的干性特征。同时研究结果显示PCK2的表达与肿瘤病人的生存期密切相关。作为恶性肿瘤再生细胞代谢的一个重要特征，PCK2有望作为新靶点用于临床肿瘤的诊断和治疗。

原文链接：

Downregulation of PCK2 remodels tricarboxylic acid cycle in tumor-repopulating cells of melanoma

原文摘要：

For cancer cells to proliferate, a balance must be built between biomass-forming, glucose-metabolized intermediates and ATP production. How intrinsic glucose carbon flow regulates this balance remains unclear. Here we show that mitochondrial phosphoenolpyruvate carboxykinase (PCK2), the hub molecule linking tricarboxylic acid (TCA) cycle, glycolysis and gluconeogenesis by conversion of mitochondrial oxaloacetate (OAA) to phosphoenolpyruvate, regulates glucose carbon flow direction in stem-like cells that repopulate tumors (tumor-repopulating cells (TRCs)). PCK2 downregulation accelerated biosynthesis and transportation of citrate from mitochondria to the cytosol, leading to cytosolic glucose carbon flow via OAA–malate–pyruvate and acetyl-CoA–fatty acid pathways in TRCs. On the other hand, downregulating PCK2 hindered fumarate carbon flows in TCA cycle, leading to attenuated oxidative phosphorylation. In pathological terms, PCK2 overexpression slowed TRC growth in vitro and impeded tumorigenesis in vivo. Overall, our work unveiled unexpected glucose carbon flows of TRCs in melanoma that have implications for targeting metabolic aspects of melanoma.