COMMD7 functions as molecular target in pancreatic ductal adenocarcinoma. Issue 2 (8th July 2016)

• Record Type: Journal Article
• Authors: You, Nan; Li, Jing; Gong, Zhenbin; Huang, Xiaobing; Wang, Weiwei; Wang, Liang; Wu, Ke; Zheng, Lu
• Is Part Of: Molecular carcinogenesis. Volume 56:Issue 2(2017:Feb.)
• Page Start: 607
• Page End: 624
• Publication Date: 2016-07-08
• Subjects: COMMD7 -- pancreatic ductal adenocarcinoma (PDAC) -- extracellular signal‐regulated kinase1/2 (ERK1/2) -- molecular target; Carcinogenesis -- Molecular aspects -- Periodicals; 616.994071
• DOI: 10.1002/mc.22520
• Languages: English
• ISSNs: 0899-1987

Abstract

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.