title: COMMD7 functions as molecular target in pancreatic ductal adenocarcinoma.
abstract: Our previous studies provided evidence that COMMD7 was associated with tumor progression in human solid cancer. Herein, we aimed to investigate its expression pattern, clinical significance, and biological function in pancreatic ductal adenocarcinoma (PDAC). We found that high COMMD7 expression was specifically detected in PDAC tissues and PDAC cell lines. In addition, COMMD7 overexpression positively correlated with histological differentiation and tumor node metastasis (TNM) stage. Patients with high COMMD7 expression had significantly poorer overall survival, and high COMMD7 expression was an independent predictor of poor prognosis. To further explore the regulatory mechanism of COMMD7, we used stable short hairpin RNA (shRNA)-mediated knockdown and divided the work into in vitro and in vivo experiments. In vitro, the anti-proliferation effects of COMMD7 inhibition were observed under long-time stress conditions, which correlated with cyclin D1 and Bcl-2 downregulation and Bax upregulation. We found that under short-time stress conditions, decreased COMMD7 expression also inhibited PDAC cell invasion in vitro which decreased the secretion of matrix metalloproteinase 2 (MMP-2). Moreover, extracellular signal-regulated kinase1/2 (ERK1/2) was identified as a direct target of COMMD7. The inhibition of ERK1/2 activity under short- or long-time stress conditions using specific inhibitors in COMMD7 inhibition cells all exhibited a strong tumorigenic role. In vivo, COMMD7 was sufficient to impair tumor growth. Our results suggest that COMMD7 plays an important role in the late progression of PDAC and is a potential novel target. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Hepatobiliary Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Nan
authors.initials: N
authors.lastname: You
authors.affiliation: Department of Hepatobiliary Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Center of Hepatobiliary Surgery of Lanzhou Army Region, Lanzhou, P. R. China.
authors.forename: Zhenbin
authors.initials: Z
authors.lastname: Gong
authors.affiliation: Department of Hepatobiliary Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Hepatobiliary Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Hepatobiliary Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Ke
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Hepatobiliary Surgery, Xinqiao Hospital, Third Military Medical University, Chongqing, P. R. China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zheng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D010179:Pancreas / Q000378:metabolism / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C554642:COMMD7 protein, human; D034741:RNA, Small Interfering
keywords: COMMD7; extracellular signal-regulated kinase1/2 (ERK1/2); molecular target; pancreatic ductal adenocarcinoma (PDAC)