Gao Shui-Ping, Sun He-Fen, Jiang Hong-Lin, Li Liang-Dong, Hu Xin, Xu Xiao-En, Jin Wei
Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Collaborative Innovation Center of Cancer Medicine, Fudan University Shanghai Cancer Center, Shanghai, 200030, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200030, China.
Tumour Biol. 2016 Jan;37(1):1279-87. doi: 10.1007/s13277-015-3878-0. Epub 2015 Aug 20.
TIM50 is an essential component of TIM23 complex and involved in protein translocating into the inner mitochondrial membrane. Here, we found that TIM50 was increased in breast cancer cells by SILAC. However, its biological functions and molecular mechanisms in breast cancer are poorly understood. To gain insight into the functions of TIM50 in breast cancer, we constructed two stably transfected cell lines and examined TIM50 expression in tissue samples. Our data showed that TIM50 expression was increased in breast cancer. The stable suppression of TIM50 expression through lentivirus-mediated shRNA was shown to inhibit the abilities of cancer cell proliferation and induce apoptosis. What is more, depletion of TIM50 could decrease mitochondrial membrane potential, which may be associated with cell viability. Taken together, our findings reveal a new role for TIM50 in regulating cell proliferation and apoptosis through decreasing mitochondrial membrane potential in breast cancer cell and suggest that TIM50 might be a potential target for controlling breast cancer progression.
TIM50是TIM23复合体的重要组成部分，参与蛋白质转运进入线粒体内膜的过程。在此，我们通过稳定同位素标记氨基酸法（SILAC）发现乳腺癌细胞中TIM50的表达增加。然而，其在乳腺癌中的生物学功能和分子机制仍知之甚少。为深入了解TIM50在乳腺癌中的功能，我们构建了两个稳定转染的细胞系，并检测了组织样本中TIM50的表达。我们的数据显示乳腺癌中TIM50表达增加。通过慢病毒介导的短发夹RNA（shRNA）稳定抑制TIM50的表达，可抑制癌细胞增殖能力并诱导凋亡。此外，TIM50的缺失会降低线粒体膜电位，这可能与细胞活力相关。综上所述，我们的研究结果揭示了TIM50在通过降低乳腺癌细胞线粒体膜电位来调节细胞增殖和凋亡方面的新作用，并表明TIM50可能是控制乳腺癌进展的潜在靶点。
