title: URGCP promotes non-small cell lung cancer invasiveness by activating the NF-κB-MMP-9 pathway.
abstract: Invasion and metastasis are main traits of tumor progression and responsible for the poor prognosis of advanced non-small cell lung cancer (NSCLC). The molecular mechanisms underlying the malignant behaviors of NSCLC remain incompletely understood. The present study demonstrate that up-regulator of cell proliferation (URGCP), a recently identified tumor-promoting gene found in several tumor types, is markedly overexpressed in human NSCLC cell lines and clinical NSCLC samples. URGCP upregulation correlates significantly with the progression and poor prognosis of this disease. In vitro and in vivo studies demonstrate that increasing URGCP expression accelerates invasion, migration, and distant metastasis of NSCLC cells whereas downregulating URGCP suppresses these malignant traits. Notably, silencing URGCP expression almost completely abrogates the metastatic ability of NSCLC cells. At the molecular level, URGCP markedly promotes MMP-9 expression by activating NF-κB signaling. Additionally, URGCP and MMP-9 expression are positively correlated in various cohorts of human NSCLC specimens, and NF-κB-activated MMP-9 expression contributes to URGCP-induced invasiveness of NSCLC cell lines. Collectively, these findings indicate that URGCP plays an important role in promoting NSCLC cell invasion and metastasis by enhancing NF-κB-activated MMP-9 expression and may serve as a potential therapeutic target and prognostic marker.
authors.affiliation: Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, China.
authors.forename: Junchao
authors.initials: J
authors.lastname: Cai
authors.affiliation: Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, China.
authors.forename: Rong
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, China.
authors.forename: Xiaonan
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, China.
authors.forename: Le
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong, China.
authors.forename: Tianyou
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, China.
authors.forename: Lishan
authors.initials: L
authors.lastname: Fang
authors.affiliation: Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, China.
authors.forename: Jueheng
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, China.
authors.forename: Xun
authors.initials: X
authors.lastname: Zhu
authors.affiliation: Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.|Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, China.
authors.forename: Mengfeng
authors.initials: M
authors.lastname: Li
authors.affiliation: State Key Laboratory of Respiratory Diseases and Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
authors.forename: Yongbo
authors.initials: Y
authors.lastname: Huang
mesh_terms: D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D005260:Female; D064593:Heterografts; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D011379:Prognosis; D015398:Signal Transduction; D016019:Survival Analysis; D014162:Transfection
chemical_list: D016328:NF-kappa B; D009363:Neoplasm Proteins; C470990:URGCP protein, human; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9
keywords: MMP-9; NF-κB signaling; URGCP; lung cancer; tumor invasion and metastasis