title: XPC inhibits NSCLC cell proliferation and migration by enhancing E-Cadherin expression.
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.
authors: Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors: Tiantian
authors: T
authors: Cui
authors: Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors: Amit Kumar
authors: AK
authors: Srivastava
authors: Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors: Chunhua
authors: C
authors: Han
authors: Department of Radiation Oncology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors: Linlin
authors: L
authors: Yang
authors: Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors: Ran
authors: R
authors: Zhao
authors: Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors: Ning
authors: N
authors: Zou
authors: Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors: Meihua
authors: M
authors: Qu
authors: Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors: Wenrui
authors: W
authors: Duan
authors: Center for Biostatistics, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors: Xiaoli
authors: X
authors: Zhang
authors: Department of Radiology, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors: Qi-En
authors: QE
authors: Wang
mesh_terms: D015820:Cadherins / Q000096:biosynthesis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D004249:DNA Damage; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D020935:MAP Kinase Signaling System; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000096:biosynthesis; D014162:Transfection
chemical_list: D015820:Cadherins; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C086984:XPC protein, human
keywords: E-Cadherin; ERK pathway; Snail; XPC; non-small-cell lung cancer