Abstract
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.
Highlights
Lung cancer is the most frequently diagnosed cancer and the leading cause of cancer death worldwide [1,2,3]
In the 20 cases of paired tissue samples, the results of western blotting showed that the normalized protein level of Transmembrane protein 17 (TMEM17) in noncancerous lung tissues (Mean ± SD = 0.9305 ± 0.1173) were significantly higher than in non-small cell lung cancer (NSCLC) specimens (Mean ± SD = 0.5902 ± 0.076, p=0.010, Figure 1A and 1B), and corresponding IHC staining results showed that TMEM17 was localized in the cytoplasm of all tested samples (Figure 1C)
Statistical analysis indicated that loss of TMEM17 expression was significantly correlated with moderate or poor histological differentiation (p=0.027, Figure 2C and 2D, Figure 2E and 2F), advanced TNM staging (p=0.006) and positive lymph node metastasis (p=0.002) in NSCLC
Summary
Lung cancer is the most frequently diagnosed cancer and the leading cause of cancer death worldwide [1,2,3]. Tumor invasion and metastasis greatly limit treatment options and account for 90% of cancer-related death [4, 5]. It is important to search for new therapeutic targets involved in the regulation of lung cancer cell invasion. Transmembrane protein 17 (TMEM17) is a newly identified 198 amino acid protein encoded by a gene mapping to human chromosome 2. We speculated that TMEM17 may be involved in the process. Kmplot.com), we found lower expression of TMEM17 significantly correlated with NSCLC patients poor survival (p=0.014, data not shown). To date, little is known on its expression pattern and molecular mechanism, especially in human lung cancer
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