title: Regulation of β-catenin transcription activity by leupaxin in hepatocellular carcinoma.
abstract: In human cancers, β-catenin is accumulated in the nucleus and activates mRNA transcription of many oncogenic genes, such as cyclin D1 and c-myc. However, the mechanism of β-catenin-mediated transcriptional activation remains largely unknown. In the present study, we identified leupaxin, an adaptor protein sharing homology with the focal adhesion protein, as a novel coactivator for β-catenin in human hepatocellular carcinoma (HCC). We show that leupaxin could interact with β-catenin and enhance its transcriptional activity through recruitment of coactivator complex, including steroid receptor coactivator 1 (SRC-1) and P300. As a result, leupaxin regulates HCC cell proliferation and cell-cycle progression in the presence of intact Wnt/β-catenin signaling. Furthermore, leupaxin is overexpressed in HCC tissues and correlated with mRNA levels of cyclin D1 and c-myc. Therefore, this is the first demonstration of a role for the leupaxin in the regulation of HCC progression, at least in part, by enhancing β-catenin transcription activity.
authors.affiliation: Department of Pediatric Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665, Kongjiang Road, Shanghai, 200092, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Pediatric Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665, Kongjiang Road, Shanghai, 200092, China.
authors.forename: Wen-Jie
authors.initials: WJ
authors.lastname: Wu
authors.affiliation: Key Laboratory of Kidney Disease Pathogenesis and Intervention of Hubei Province, College of Medicine, Hubei Polytechnic University, Huangshi, Hubei, 435003, People's Republic of China.
authors.forename: Gang
authors.initials: G
authors.lastname: Hu
authors.affiliation: Key Laboratory of Kidney Disease Pathogenesis and Intervention of Hubei Province, College of Medicine, Hubei Polytechnic University, Huangshi, Hubei, 435003, People's Republic of China.
authors.forename: Xin
authors.initials: X
authors.lastname: Yu
authors.affiliation: Key Laboratory of Kidney Disease Pathogenesis and Intervention of Hubei Province, College of Medicine, Hubei Polytechnic University, Huangshi, Hubei, 435003, People's Republic of China.
authors.forename: Ge-Shu
authors.initials: GS
authors.lastname: Yu
authors.affiliation: Department of Anesthesiology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (SJTU-SM), 197, Rui Jin Er Road, Shanghai, 200025, People's Republic of China.
authors.forename: Han
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, Jianli Second People's Hospital, Jianli, Hubei, 433325, People's Republic of China.
authors.forename: Ming-Liang
authors.initials: ML
authors.lastname: Yang
authors.affiliation: Key Laboratory of Kidney Disease Pathogenesis and Intervention of Hubei Province, College of Medicine, Hubei Polytechnic University, Huangshi, Hubei, 435003, People's Republic of China. liubin3575630@163.com.
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Pediatric Surgery, Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, No. 1665, Kongjiang Road, Shanghai, 200092, China. zhixiangwu@yahoo.com.
authors.forename: Zhi-Xiang
authors.initials: ZX
authors.lastname: Wu
mesh_terms: D015153:Blotting, Western; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D055785:Gene Knockdown Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D014158:Transcription, Genetic; D051176:beta Catenin / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C495270:CTNNB1 protein, human; D015815:Cell Adhesion Molecules; C112251:LPXN protein, human; D010750:Phosphoproteins; D051176:beta Catenin
keywords: Coactivator; Hepatocellular carcinoma (HCC); Leupaxin; Transcription activity; β-catenin