Zhang Xiupeng, Zhang Yong, Miao Yuan, Zhou Haijing, Jiang Guiyang, Wang Enhua
Department of Pathology, College of Basic Medical Sciences and The First Affiliated Hospital, China Medical University, Shenyang, China.
Department of Pathology, Cancer Hospital of China Medical University, Shenyang, China.
Oncotarget. 2017 Aug 7;8(41):70685-70694. doi: 10.18632/oncotarget.19977. eCollection 2017 Sep 19.
Transmembrane protein 17(TMEM17) is a newly identified protein, its expression pattern and clinicopathological relevance is still unclear. In this study, western blot assay was performed in 20 paired lung cancer samples and found that TMEM17 protein levels were lower in lung cancer tissues than that in the corresponding normal lung tissues (p=0.010). Immunohistochemistry staining in 143 cases lung cancer specimens also showed that TMEM17 expression in lung cancer tissues were significantly lower than adjacent normal lung tissues (35.7% 63.2%, p<0.001). And negative TMEM17 expression was significantly associated with poor histological differentiation (p=0.027), advanced TNM stages (p=0.006), positive lymph node metastasis (p=0.002) and poor prognosis (p=0.002). After overexpressing TMEM17, levels of p-ERK and its downstream molecules, p-P90RSK and Snail, were down-regulated, while levels of Occludin and Zo-1 were up-regulated, which result in the inhibition of invasion and migration ability of lung cancer cells. The effects were reversed by the incorporation of specific ERK inhibitor PD98059. In conclusion, loss of TMEM17 correlates with the development of non-small cell lung cancer (NSCLC) and predicts adverse clinical outcome of NSCLC patients. The effect of TMEM17 on inhibiting invasion and migration may attribute to restoring Occludin and Zo-1 expression through inactivating ERK-P90RSK-Snail pathway.
跨膜蛋白17（TMEM17）是一种新发现的蛋白，其表达模式及与临床病理的相关性仍不清楚。本研究对20对肺癌样本进行了蛋白质印迹分析，发现肺癌组织中TMEM17蛋白水平低于相应的正常肺组织（p = 0.010）。对143例肺癌标本进行免疫组织化学染色也显示，肺癌组织中TMEM17的表达明显低于邻近正常肺组织（35.7%对63.2%，p<0.001）。TMEM17阴性表达与组织学分化差（p = 0.027）、TNM分期晚（p = 0.006）、淋巴结转移阳性（p = 0.002）及预后差（p = 0.002）显著相关。过表达TMEM17后，p-ERK及其下游分子p-P90RSK和Snail的水平下调，而闭合蛋白和紧密连接蛋白1的水平上调，这导致肺癌细胞侵袭和迁移能力受到抑制。加入特异性ERK抑制剂PD98059可逆转这些效应。总之，TMEM17缺失与非小细胞肺癌（NSCLC）的发生发展相关，并可预测NSCLC患者的不良临床结局。TMEM17抑制侵袭和迁移的作用可能归因于通过使ERK-P90RSK-Snail通路失活来恢复闭合蛋白和紧密连接蛋白1的表达。
