State Key Laboratory for Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, P. R. China.
Translational Medicine Laboratory, Chinese PLA General Hospital, Beijing, P. R. China.
Cell Death Dis. 2021 Nov 16;12(12):1086. doi: 10.1038/s41419-021-04369-1.
Transmembrane protein (TMEM) is a family of protein that spans cytoplasmic membranes and allows cell-cell and cell-environment communication. Dysregulation of TMEMs has been observed in multiple cancers. However, little is known about TMEM116 in cancer development. In this study, we demonstrate that TMEM116 is highly expressed in non-small-cell lung cancer (NSCLC) tissues and cell lines. Inactivation of TMEM116 reduced cell proliferation, migration and invasiveness of human cancer cells and suppressed A549 induced tumor metastasis in mouse lungs. In addition, TMEM116 deficiency inhibited PDK1-AKT-FOXO3A signaling pathway, resulting in accumulation of TAp63, while activation of PDK1 largely reversed the TMEM116 deficiency induced defects in cancer cell motility, migration and invasive. Together, these results demonstrate that TMEM116 is a critical integrator of oncogenic signaling in cancer metastasis.
跨膜蛋白 (TMEM) 是一类跨越细胞质膜的蛋白家族，允许细胞间和细胞与环境间的通讯。TMEM 在多种癌症中存在失调。然而，关于 TMEM116 在癌症发展中的作用知之甚少。在这项研究中，我们证明 TMEM116 在非小细胞肺癌 (NSCLC) 组织和细胞系中高度表达。TMEM116 的失活减少了人癌细胞的增殖、迁移和侵袭，并抑制了 A549 在小鼠肺部诱导的肿瘤转移。此外，TMEM116 缺失抑制了 PDK1-AKT-FOXO3A 信号通路，导致 TAp63 的积累，而 PDK1 的激活则在很大程度上逆转了 TMEM116 缺失引起的癌细胞运动、迁移和侵袭缺陷。综上所述，这些结果表明 TMEM116 是癌症转移中致癌信号的关键整合因子。
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