CARF activates beta-catenin/TCF signaling in the hepatocellular carcinoma.
Overactivation of Ras signaling is very common in the hepatocellular carcinoma (HCC) due to its constitutive active mutation, which makes it a big challenge to target Ras signaling. Therefore, identifying effectors downstream of Ras signaling would benefit the development of novel therapeutic strategies. In this study, it was found that the expression of CARF (collaborate of ARF) was induced by oncogenic RasV12. The expression of CARF was up-regulated in both HCC mouse model (Alb-Cre; P53f/f; Loxp-Stop-Loxp-RasG12D) and human HCC clinical samples. Overexpression of CARF promoted the growth and migration of HCC cells, while knocking down the expression of CARF inhibited the growth and migration of HCC cells. In the mechanism study, CARF was found to interact with beta-catenin, impaired the interaction between beta-catenin and ICAT, and activated beta-catenin/TCF signaling. Moreover, knocking down the expression of CARF inhibited the tumorigenesis in the HCC mouse model. Taken together, this study revealed the oncogenic functions of CARF in the tumorigenesis of HCC by activating beta-catenin/TCF signaling, and suggested CARF might be a therapeutic target in the treatment of HCC.
Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, PR China.
Xin
X
Fan
Department of Gynecology and Obstetrics, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, PR China.
Xiaoyan
X
Ma
Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, PR China.
Lei
L
Cui
Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, PR China.
Shengchun
S
Dang
Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, PR China.
Jianguo
J
Qu
Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, PR China.
Jianxin
J
Zhang
Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, PR China.
Xuqing
X
Wang
Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, PR China.
Zhengfa
Z
Mao
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008822:Mice, Transgenic; D034622:RNA Interference; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C539004:CDKN2AIP protein, human; C495270:CTNNB1 protein, human; C411982:CTNNBIP1 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D016601:RNA-Binding Proteins; D051820:TCF Transcription Factors; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin; C000626289:collaborator of ARF protein, mouse
CARF; HCC; RasV12; beta-catenin/TCF signaling