CARF activates beta-catenin/TCF signaling in the hepatocellular carcinoma

Xin Fan; Xiaoyan Ma; Lei Cui; Shengchun Dang; Jianguo Qu; Jianxin Zhang; Xuqing Wang; Zhengfa Mao

doi:10.18632/oncotarget.13138

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Research Papers:

CARF activates beta-catenin/TCF signaling in the hepatocellular carcinoma

Xin Fan, Xiaoyan Ma, Lei Cui, Shengchun Dang, Jianguo Qu, Jianxin Zhang, Xuqing Wang and Zhengfa Mao _

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Oncotarget. 2016; 7:80404-80414. https://doi.org/10.18632/oncotarget.13138

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Abstract

Xin Fan1,*, Xiaoyan Ma2,*, Lei Cui1, Shengchun Dang1, Jianguo Qu1, Jianxin Zhang1, Xuqing Wang1, Zhengfa Mao1

1Department of General Surgery, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, PR China

2Department of Gynecology and Obstetrics, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu Province, PR China

*These authors contributed equally to this work

Correspondence to:

Zhengfa Mao, email: [email protected]

Keywords: CARF, HCC, beta-catenin/TCF signaling, Ras^V12

Received: June 04, 2016 Accepted: October 14, 2016 Published: November 05, 2016

ABSTRACT

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 Ras^V12. The expression of CARF was up-regulated in both HCC mouse model (Alb-Cre; P53^f/f; Loxp-Stop-Loxp-Ras^G12D) 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.

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Research Papers:

CARF activates beta-catenin/TCF signaling in the hepatocellular carcinoma

Abstract