URGCP promotes non-small cell lung cancer invasiveness by activating the NF-κB-MMP-9 pathway
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Junchao Cai1,2,*, Rong Li1,2,*, Xiaonan Xu1,2, Le Zhang1,2, Shanshan Wu1,2, Tianyou Yang3, Lishan Fang1,2, Jueheng Wu1,2, Xun Zhu1,2, Mengfeng Li1,2, Yongbo Huang4
1Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China
2Key Laboratory of Tropical Disease Control, Sun Yat-sen University, Ministry of Education, Guangzhou, China
3Department of Pediatric Surgery, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangdong, China
4State Key Laboratory of Respiratory Diseases and Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China
*These authors have contributed equally to this work
Yongbo Huang, e-mail: [email protected]
Mengfeng Li, e-mail: [email protected]
Keywords: lung cancer, URGCP, tumor invasion and metastasis, NF-κB signaling, MMP-9
Received: April 09, 2015 Accepted: September 15, 2015 Published: September 28, 2015
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.
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