Enhanced expression of cholecystokinin-2 receptor promotes the progression of colon cancer through activation of focal adhesion kinase
Corresponding Author
Hong-Gang Yu
Department of Gastroenterology, Renmin Hospital of Wuhan University, 430060 Wuhan, China
Institute for Gastroenterology and Hepatology, Wuhan University Medical School, 430060 Wuhan, China
Fax: +86-27-88042292
Department of Gastroenterology, Renmin Hospital of Wuhan University, Jiefang road 238, 430060 Wuhan, ChinaSearch for more papers by this authorShi-Lun Tong
Institute for Gastroenterology and Hepatology, Wuhan University Medical School, 430060 Wuhan, China
Search for more papers by this authorYou-Ming Ding
Institute for Gastroenterology and Hepatology, Wuhan University Medical School, 430060 Wuhan, China
Search for more papers by this authorJian Ding
Institute for Gastroenterology and Hepatology, Wuhan University Medical School, 430060 Wuhan, China
Search for more papers by this authorXiang-Min Fang
Department of Gastroenterology, The Third Hospital of Wuhan, 430060 Wuhan, China
Search for more papers by this authorXian-Feng Zhang
Institute for Gastroenterology and Hepatology, Wuhan University Medical School, 430060 Wuhan, China
Search for more papers by this authorZhu-Jun Liu
Institute for Gastroenterology and Hepatology, Wuhan University Medical School, 430060 Wuhan, China
Search for more papers by this authorYan-Hong Zhou
Institute for Gastroenterology and Hepatology, Wuhan University Medical School, 430060 Wuhan, China
Search for more papers by this authorQi-Sheng Liu
Institute for Gastroenterology and Hepatology, Wuhan University Medical School, 430060 Wuhan, China
Search for more papers by this authorHe-Sheng Luo
Department of Gastroenterology, Renmin Hospital of Wuhan University, 430060 Wuhan, China
Institute for Gastroenterology and Hepatology, Wuhan University Medical School, 430060 Wuhan, China
Search for more papers by this authorJie-Ping Yu
Department of Gastroenterology, Renmin Hospital of Wuhan University, 430060 Wuhan, China
Institute for Gastroenterology and Hepatology, Wuhan University Medical School, 430060 Wuhan, China
Search for more papers by this authorCorresponding Author
Hong-Gang Yu
Department of Gastroenterology, Renmin Hospital of Wuhan University, 430060 Wuhan, China
Institute for Gastroenterology and Hepatology, Wuhan University Medical School, 430060 Wuhan, China
Fax: +86-27-88042292
Department of Gastroenterology, Renmin Hospital of Wuhan University, Jiefang road 238, 430060 Wuhan, ChinaSearch for more papers by this authorShi-Lun Tong
Institute for Gastroenterology and Hepatology, Wuhan University Medical School, 430060 Wuhan, China
Search for more papers by this authorYou-Ming Ding
Institute for Gastroenterology and Hepatology, Wuhan University Medical School, 430060 Wuhan, China
Search for more papers by this authorJian Ding
Institute for Gastroenterology and Hepatology, Wuhan University Medical School, 430060 Wuhan, China
Search for more papers by this authorXiang-Min Fang
Department of Gastroenterology, The Third Hospital of Wuhan, 430060 Wuhan, China
Search for more papers by this authorXian-Feng Zhang
Institute for Gastroenterology and Hepatology, Wuhan University Medical School, 430060 Wuhan, China
Search for more papers by this authorZhu-Jun Liu
Institute for Gastroenterology and Hepatology, Wuhan University Medical School, 430060 Wuhan, China
Search for more papers by this authorYan-Hong Zhou
Institute for Gastroenterology and Hepatology, Wuhan University Medical School, 430060 Wuhan, China
Search for more papers by this authorQi-Sheng Liu
Institute for Gastroenterology and Hepatology, Wuhan University Medical School, 430060 Wuhan, China
Search for more papers by this authorHe-Sheng Luo
Department of Gastroenterology, Renmin Hospital of Wuhan University, 430060 Wuhan, China
Institute for Gastroenterology and Hepatology, Wuhan University Medical School, 430060 Wuhan, China
Search for more papers by this authorJie-Ping Yu
Department of Gastroenterology, Renmin Hospital of Wuhan University, 430060 Wuhan, China
Institute for Gastroenterology and Hepatology, Wuhan University Medical School, 430060 Wuhan, China
Search for more papers by this authorAbstract
Focal adhesion kinase (FAK) is suggested to be intimately involved in the progression of malignancies. Our previous research has demonstrated that activation of cholecystokinin-2 receptor (CCK2R) by gastrin stimulates a rapid activation of FAK pathway in human colon cancer cells. The purpose of this study is to determine the role of CCK2R and FAK in the progression of colon cancer. In this study, matched tissue samples of primary colon cancer and adjacent normal colon mucosa from the same patient were collected from 45 patients with colon cancer undergoing surgical resection. The gastrin expression was detected using reverse transcription polymerase chain reaction (RT-PCR). The CCK2R expression was examined by in situ hybridization and RT-PCR. The expression of FAK and phosphorylated FAK at tyrosine 397 (phospho-FAK) were detected using immunohistochemistry and immunoblotting. Colo320 and SW787, 2 colon cancer cell lines with or without CCK2R expression, were recruited in this study. Antisense oligonucleotide of FAK was used to block the expression of FAK. Invasiveness and motility of colon cancer cells were detected by Boyden chamber. In this series, enhanced expression of gastrin, CCK2R, FAK and phospho-FAK were observed in colon cancer tissues. CCK2R expression correlated with expression of phospho-FAK. Coexpression of CCK2R and phospho-FAK associated with invasion and lymph node metastasis. Increased invasion and motility was induced by gastrin in Colo320 cells. Overexpression of CCK2R by stable transfection of CCK2R plasmid amplified this increase and incubation with 1 μM L-365,260, a specific CCK2R antagonist, completely inhibited the effect of gastrin. FAK antisense largely blocked the increase of invasion and motility in Colo320 cells. Our data represent the evidence for the CCK2R regulating invasion and motility of colon cancer cells, and support a role of CCK2R in the progression of colon cancer. FAK play a critical role in this CCK2R-mediated effect. © 2006 Wiley-Liss, Inc.
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