线粒体功能损伤是在癌症中普遍存在的现象。然而，其促进癌肿进展的机制还不清楚。EMT是参与胚胎发育、创伤修复和器官纤维化等生理病理过程的重要事件。越来越多的研究表明，EMT是上皮性质的癌细胞组织浸润和远端转移的重要途径之一。目前，线粒体功能损伤与EMT是否存在联系及其在癌症发展过程中的作用还不清楚。

线粒体具有自己的基因组和特异性的基因表达系统。线粒体基因组编码了组成线粒体呼吸链酶复合体的13个亚基以及线粒体特有的rRNAs和tRNAs。TUFM是核基因编码的调控线粒体蛋白翻译的关键因子之一，其参与了线粒体基因蛋白翻译过程中的氨基酸延伸和密码子-反密码子以及氨基酸-tRNA配对的校对。

在该研究中，宋建国组的博士研究生贺凯和郭晓杰等人发现，在肺癌组织中TUFM的表达水平与上皮细胞标志蛋白E-cadherin呈正相关性而与肺癌的进展呈负相关性。敲低TUFM抑制了肺癌细胞线粒体基因编码蛋白的表达，引起了线粒体功能损伤并促进了ROS的生成。TUFM下调引起的细胞能量和氧化胁迫导致了AMPK的激活。活化的AMPK能进一步磷酸化GSK3b，进而促进b-catenin的核转运和细胞核基因的表达，最终诱导肺癌细胞发生EMT并促进肺癌细胞的迁移、浸润和抗失巢凋亡。因此，核基因蛋白TUFM的下调抑制了线粒体基因的表达，进而促使AMPK-GSK3b-b-catenin通路的激活，最终影响核基因的表达并诱导肺癌细胞EMT和相关细胞功能的改变。

综上所述，该工作揭示了线粒体功能损伤与EMT的分子联系并为人们深入了解线粒体功能损伤促进癌症发展的机制提供了重要信息。

原文摘要： Mitochondrial dysfunction and epithelial-to-mesenchymal transition (EMT) play important roles in cancer development and metastasis. However, very little is known about the connection between mitochondrial dysfunction and EMT. Tu translation elongation factor, mitochondrial (TUFM), a key factor in the translational expression of mitochondrial DNA, plays an important role in the control of mitochondrial function. Here, we show that TUFM is downregulated in human cancer tissues. TUFM expression level was positively correlated with that of E-cadherin and decreased significantly during the progression of human lung cancer. TUFM knockdown induced EMT, reduced mitochondrial respiratory chain activity, and increased glycolytic function and the production of reactive oxygen species (ROS). Mechanistically, TUFM knockdown activated AMPK and phosphorylated GSK3β and increased the nuclear accumulation of β-catenin, leading to the induction of EMT and increased migration and metastasis of A549 lung cancer cells. Although TUFM knockdown also induced EMT of MCF7 breast cancer cells, the underlying mechanism appeared somewhat different from that in lung cancer cells. Our work identifies TUFM as a novel regulator of EMT and suggests a molecular link between mitochondrial dysfunction and EMT induction DOI：10.1007/s00018-015-2122-9