TMEM17 depresses invasion and metastasis in lung cancer cells via ERK signaling pathway.
TMEM17 depresses invasion and metastasis in lung cancer cells via ERK signaling pathway.
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TMEM17通过ERK信号通路抑制肺癌细胞的侵袭和转移
DOI：
10.18632/oncotarget.19977
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发表时间：
2017-09-19
期刊：
影响因子：
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通讯作者：
Wang E
中科院分区：
文献类型：
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作者：
Zhang X;Zhang Y;Miao Y;Zhou H;Jiang G;Wang E
跨膜蛋白17（Transmembrane protein 17，TMEM 17）是一种新发现的蛋白质，其表达模式和临床病理意义尚不清楚。在本研究中，在20对肺癌样本中进行蛋白质印迹分析，发现肺癌组织中的TMEM 17蛋白水平低于相应的正常肺组织（p=0.010）。143例肺癌组织中TMEM 17的阳性表达率为35.7%，显著低于癌旁正常肺组织的63.2%（P<0.001）。TMEM 17阴性表达与组织分化差（p=0.027）、TNM分期晚（p=0.006）、淋巴结转移阳性（p=0.002）和预后差（p=0.002）显著相关。过表达TMEM 17后，p-ERK及其下游分子p-P90 RSK和Snail表达下调，Occludin和Zo-1表达上调，从而抑制肺癌细胞的侵袭和迁移能力。通过掺入特异性ERK抑制剂PD 98059，该作用被逆转。总之，TMEM 17的缺失与非小细胞肺癌（NSCLC）的发展相关，并预测NSCLC患者的不良临床结果。TMEM 17抑制细胞侵袭和迁移的作用可能是通过抑制ERK-P90 RSK-Snail通路恢复Occludin和Zo-1的表达。
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% vs 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.