Zhang Shuai, He Yunlong, Xuan Qijia, Ling Xiaodong, Men Kaiya, Zhao Xu, Xue Dinglong, Li Ling, Zhang Yingying
Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
Department of Radiation Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
Cancer Sci. 2022 Jun;113(6):1999-2007. doi: 10.1111/cas.15341. Epub 2022 Apr 1.
Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases and has the highest mortality rate among all solid tumors. It is characterized by early metastasis, and investigations of the molecular mechanisms underlying the progression and metastasis of NSCLC are urgently needed for the development of therapeutic targets. Here, we report that the transmembrane protein TMEM139 is significantly downregulated in NSCLC and that reduced expression of TMEM139 is correlated with a poor prognosis in NSCLC patients. Mechanistically, we found that TMEM139 directly interacts with E-cadherin at the plasma membrane and at focal adhesion sites. Moreover, TMEM139 can prevent the lysosomal degradation of E-cadherin, which inhibits epithelial-mesenchymal transition, migration and invasion of NSCLC cells both in vitro and in vivo. Our study not only expands our understanding of NSCLC metastasis but also provides a foundation to develop novel therapeutic strategies.
非小细胞肺癌（NSCLC）约占所有肺癌病例的85%，在所有实体瘤中死亡率最高。其特点是早期转移，因此迫切需要对NSCLC进展和转移的分子机制进行研究，以开发治疗靶点。在此，我们报告跨膜蛋白TMEM139在NSCLC中显著下调，且TMEM139表达降低与NSCLC患者的不良预后相关。从机制上讲，我们发现TMEM139在质膜和粘着斑位点与E-钙粘蛋白直接相互作用。此外，TMEM139可防止E-钙粘蛋白的溶酶体降解，从而在体外和体内抑制NSCLC细胞的上皮-间质转化、迁移和侵袭。我们的研究不仅扩展了我们对NSCLC转移的理解，也为开发新的治疗策略提供了基础。
