FAM98A promotes proliferation of non-small cell lung cancer cells via the P38-ATF2 signaling pathway
Authors Zheng R, Liu Q, Wang T, Wang L, Zhang Y
Received 21 January 2018
Accepted for publication 13 April 2018
Published 27 July 2018 Volume 2018:10 Pages 2269—2278
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 4
Editor who approved publication: Professor Harikrishna Nakshatri
Rui Zheng,1 Quanbo Liu,1 Tianxu Wang,1 Lili Wang,1 Yong Zhang2
1Department of Respiratory Medicine, Shengjing Hospital of China Medical University, Shenyang, China; 2Department of Pathology, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang, China
Background: FAM98A, a novel protein, is expressed in ovarian and colorectal cancer tissues. However, the association between FAM98A expression and the clinicopathological characteristics of non-small cell lung cancer (NSCLC) remains undetermined.
Materials and methods: The FAM98A expression pattern was determined in NSCLC samples and corresponding adjacent normal lung tissues using immunohistochemical staining and Western blotting. The association of FAM98A expression with clinicopathological characteristics was measured in 131 NSCLC samples. Finally, the overexpression and inhibition of FAM98A was performed in the A549 and SPC-A1 cell lines to explore its role in the development of lung cancer.
Results: Western blot analysis of 20 paired NSCLC samples showed that expression of FAM98A was higher in lung cancer tissues than in the corresponding adjacent normal lung tissues (p<0.05). Immunohistochemical staining of 128 NSCLC specimens showed that expression of FAM98A was significantly higher in lung cancer samples than in adjacent normal lung tissues (118/128 vs 10/128; p<0.001). Positive expression of FAM98A was significantly related to tumor TNM stage (p<0.05) and lymph node metastasis (p<0.001). Additionally, overexpression of FAM98A induced an increase in the expression of phosphorylated P38, phosphorylated ATF2, and cyclin D1, which promoted proliferation of lung cancer cells. Correspondingly, the effects of FAM98A overexpression were reversed by administration of a specific inhibitor of phosphorylated P38.
Conclusion: FAM98A was overexpressed in the cytoplasm of NSCLC samples and correlated with advanced TNM staging and lymph node metastasis. Thus, FAM98A increases the expression of cyclin D1 by activating the P38-ATF2 signaling pathway and subsequently enhancing tumor cell proliferation; these results are promising and need further validation.
Keywords: ATF2, TNM stage, lymph node metastasis
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