XPC inhibits NSCLC cell proliferation and migration by enhancing E-Cadherin expression

// Tiantian Cui 1 , Amit Kumar Srivastava 1 , Chunhua Han 1 , Linlin Yang 2 , Ran Zhao 1 , Ning Zou 1 , Meihua Qu 1 , Wenrui Duan 3 , Xiaoli Zhang 4 and Qi-En Wang 1 1 Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH, USA 2 Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA 3 Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA 4 Center for Biostatistics, The Ohio State University Wexner Medical Center, Columbus, OH, USA Correspondence to: Qi-En Wang, email: // Keywords : XPC, E-Cadherin, non-small-cell lung cancer, Snail, ERK pathway Received : December 28, 2014 Accepted : February 13, 2015 Published : March 12, 2015 Abstract Xeroderma pigmentosum complementation group C (XPC) protein is an important DNA damage recognition factor in nucleotide excision repair. Deletion of XPC is associated with early stages of human lung carcinogenesis, and reduced XPC mRNA levels predict poor patient outcome for non-small cell lung cancer (NSCLC). However, the mechanisms linking loss of XPC expression and poor prognosis in lung cancer are still unclear. Here, we report evidence that XPC silencing drives proliferation and migration of NSCLC cells by down-regulating E-Cadherin. XPC knockdown enhanced proliferation and migration while decreasing E-Cadherin expression in NSCLC cells with an epithelial phenotype. Restoration of E-Cadherin in these cells suppressed XPC knockdown-induced cell growth both in vitro and in vivo . Mechanistic studies showed that the loss of XPC repressed E-Cadherin expression by activating the ERK pathway and upregulating Snail expression. Our findings indicate that XPC silencing-induced reduction of E-Cadherin expression contributes, at least in part, to the poor outcome of NSCLC patients with low XPC expression.