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TIMM50 promotes tumor progression via ERK signaling and predicts poor prognosis of non‐small cell lung cancer patients
Author(s) -
Zhang Xiupeng,
Han Shuai,
Zhou Haijing,
Cai Lin,
Li Jingduo,
Liu Nan,
Liu Yang,
Wang Liang,
Fan Chuifeng,
Li Ailin,
Miao Yuan
Publication year - 2019
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22969
Subject(s) - biology , mapk/erk pathway , cancer research , cyclin d1 , lung cancer , cancer , blot , cell growth , immunohistochemistry , metastasis , phosphorylation , cell cycle , medicine , microbiology and biotechnology , immunology , gene , biochemistry , genetics
TIMM50 (Translocase of the inner mitochondrial membrane 50), also called TIM50, plays an essential role in mitochondrial membrane transportation. The existing literature suggests that TIMM50 may perform as an oncogenetic protein in breast cancer. However, the molecular mechanism, especially in human non‐small cell lung cancer (NSCLC), is uncertain to date. In the present study, using immunohistochemistry, we found that TIMM50 expression significantly correlated with larger tumor size ( P = 0.049), advanced TNM stage ( P = 0.001), positive regional lymph node metastasis ( P = 0.007), and poor overall survival ( P = 0.001). Proliferation and invasion assay showed that TIMM50 dramatically promoted the ability of proliferation and invasion of NSCLC cells. Subsequent Western blotting results revealed that TIMM50 enhanced the expression of Cyclin D1 and Snail, and inhibited the expression of E‐cadherin. Moreover, TIMM50 facilitated the expression of phosphorylated ERK and P90RSK. Incorporation of ERK inhibitor counteracted the upregulating expression of CyclinD1, and Snail, and downregulating expression of E‐cadherin expression induced by TIMM50 overexpression. In conclusion, our data indicated that TIMM50 facilitated tumor proliferation and invasion of NSCLC through enhancing phosphorylation of its downstream ERK/P90RSK signaling pathway. We speculated that TIMM50 might be a useful prognosis marker of NSCLC patients.