title: Inhibition of CCAR1, a Coactivator of β-Catenin, Suppresses the Proliferation and Migration of Gastric Cancer Cells.
abstract: The aberrant activation of Wnt signaling has been implicated in a variety of human cancers, including gastric cancer. Given the current hypothesis that cancer arises from cancer stem cells (CSCs), targeting the critical signaling pathways that support CSC self-renewal appears to be a useful approach for cancer therapy. Cell cycle and apoptosis regulator 1 (CCAR1) is a transcriptional coactivator which has been shown to be a component of Wnt/β-catenin signaling, and which plays an important role in transcriptional regulation by β-catenin. However, the function and clinical significance of CCAR1 in gastric cancer have not been elucidated. Here, we show that elevated CCAR1 nuclear expression correlates with the occurrence of gastric cancer. In addition, RNAi-mediated CCAR1 reduction not only suppressed the cell growth and increased apoptosis in AGS and MKN28 cells, but also reduced the migration and invasion ability of these cells. Furthermore, an in vivo xenograft assay revealed that the expression level of CCAR1 was critical for tumorigenesis. Our data demonstrates that CCAR1 contributes to carcinogenesis in gastric cancer and is required for the survival of gastric cancer cells. Moreover, CCAR1 may serve as a diagnostic marker and a potential therapeutic target.
authors.affiliation: Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Chiayi 61303, Taiwan. cgmh3621@adm.cgmh.org.tw.|College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan. cgmh3621@adm.cgmh.org.tw.
authors.forename: Te-Sheng
authors.initials: TS
authors.lastname: Chang
authors.affiliation: Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Chiayi 61303, Taiwan. wkliang@adm.cgmh.org.tw.|College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan. wkliang@adm.cgmh.org.tw.
authors.forename: Kuo-Liang
authors.initials: KL
authors.lastname: Wei
authors.affiliation: Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Chiayi 61303, Taiwan. cmusickimo@yahoo.com.tw.
authors.forename: Chung-Kuang
authors.initials: CK
authors.lastname: Lu
authors.affiliation: Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Chiayi 61303, Taiwan. a12509@cgmh.org.tw.|College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan. a12509@cgmh.org.tw.
authors.forename: Yi-Hsing
authors.initials: YH
authors.lastname: Chen
authors.affiliation: Department of Life Science, National Chung Cheng University, Chiayi 62102, Taiwan. s26136282@livemail.tw.
authors.forename: Ying-Tung
authors.initials: YT
authors.lastname: Cheng
authors.affiliation: Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Chiayi 61303, Taiwan. ma1898@adm.cgmh.org.tw.|College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan. ma1898@adm.cgmh.org.tw.
authors.forename: Shui-Yi
authors.initials: SY
authors.lastname: Tung
authors.affiliation: Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Chiayi 61303, Taiwan. gi0005@adm.cgmh.org.tw.|College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan. gi0005@adm.cgmh.org.tw.
authors.forename: Cheng-Shyong
authors.initials: CS
authors.lastname: Wu
authors.affiliation: Department of Life Science, National Chung Cheng University, Chiayi 62102, Taiwan. biomkc@ccu.edu.tw.
authors.forename: Ming-Ko
authors.initials: MK
authors.lastname: Chiang
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008875:Middle Aged; D011379:Prognosis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; C477529:CCAR1 protein, human; D018797:Cell Cycle Proteins; D034741:RNA, Small Interfering; D051176:beta Catenin
keywords: CCAR1; Wnt signaling; gastric cancer; metastasis; β-catenin