Shuhai Chen1, Xiaoliang Kang1, Guangwei Liu2, Bingyuan Zhang1, Xiao Hu1, Yujie Feng3. 1. Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266003, Shandong, China. 2. Department of Outpatient, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266003, Shandong, China. 3. Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Qingdao University, No. 16 Jiangsu Road, Qingdao, 266003, Shandong, China. fengyj1943@163.com.
Abstract
BACKGROUND: Cholangiocarcinoma is one of the most deadly malignant tumors characterized by a tendency of local invasiveness and metastasis at the early phase, high recurrence rate, and difficulty in treatment. Alpha7-nicotinic acetylcholine receptor (α7-nAChR) is highly expressed in a variety of tumors, including cholangiocarcinoma, and may promote tumor progression, but the mechanisms are largely unknown. AIMS: Our study is the first to expound upon the role that α7-nAChR plays in cholangiocarcinoma. METHODS: We assessed 50 human cholangiocarcinoma tissue samples and 20 normal biliary samples using immunohistochemical staining to find the correlation between α7-nAChR expression and clinicopathological characteristics. We used human cholangiocarcinoma cell lines QBC939 and RBE and α7-nAChR gene knockdown RBE cell lines generated by shRNA lentivirus transfection to investigate the biological functions of α7-nAChR in proliferation, apoptosis, migration, and invasiveness in vitro. Further, western blotting was used to detect apoptosis and epithelial-mesenchymal transition (EMT)-related signaling proteins. Cholangiocarcinoma xenografts in nude mice were used for tumorigenicity assays in vivo. RESULTS: The expression of α7-nAChR was high in cholangiocarcinoma tissues and was closely related to a shorter survival time in patients. α7-nAChR knockdown decreased cell proliferation ability, increased early apoptosis, and weakened cell migration and invasion. Apoptosis-related proteins and components of the EMT process were altered after α7-nAChR knockdown. Moreover, nude mice xenograft experiments confirmed that α7-nAChR could promote cholangiocarcinoma in vitro. CONCLUSIONS: Overexpression of α7-nAChR induces cholangiocarcinoma progression by blocking apoptosis and promoting the EMT process. As an effective molecular biomarker and prognostic factor, α7-nAChR is a promising therapeutic target in cholangiocarcinoma.
BACKGROUND:Cholangiocarcinoma is one of the most deadly malignant tumors characterized by a tendency of local invasiveness and metastasis at the early phase, high recurrence rate, and difficulty in treatment. Alpha7-nicotinic acetylcholine receptor (α7-nAChR) is highly expressed in a variety of tumors, including cholangiocarcinoma, and may promote tumor progression, but the mechanisms are largely unknown. AIMS: Our study is the first to expound upon the role that α7-nAChR plays in cholangiocarcinoma. METHODS: We assessed 50 humancholangiocarcinoma tissue samples and 20 normal biliary samples using immunohistochemical staining to find the correlation between α7-nAChR expression and clinicopathological characteristics. We used humancholangiocarcinoma cell lines QBC939 and RBE and α7-nAChR gene knockdown RBE cell lines generated by shRNA lentivirus transfection to investigate the biological functions of α7-nAChR in proliferation, apoptosis, migration, and invasiveness in vitro. Further, western blotting was used to detect apoptosis and epithelial-mesenchymal transition (EMT)-related signaling proteins. Cholangiocarcinoma xenografts in nude mice were used for tumorigenicity assays in vivo. RESULTS: The expression of α7-nAChR was high in cholangiocarcinoma tissues and was closely related to a shorter survival time in patients. α7-nAChR knockdown decreased cell proliferation ability, increased early apoptosis, and weakened cell migration and invasion. Apoptosis-related proteins and components of the EMT process were altered after α7-nAChR knockdown. Moreover, nude mice xenograft experiments confirmed that α7-nAChR could promote cholangiocarcinoma in vitro. CONCLUSIONS: Overexpression of α7-nAChR induces cholangiocarcinoma progression by blocking apoptosis and promoting the EMT process. As an effective molecular biomarker and prognostic factor, α7-nAChR is a promising therapeutic target in cholangiocarcinoma.
Authors: Alberto M Martelli; Irene Faenza; Anna Maria Billi; Lucia Manzoli; Camilla Evangelisti; Federica Falà; Lucio Cocco Journal: Cell Signal Date: 2006-03-03 Impact factor: 4.315