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Liver Cancer: WISP3 Suppresses Hepatocellular Carcinoma Progression by Negative Regulation of β-catenin/TCF/LEF Signalling

Liver Cancer: WISP3 Suppresses Hepatocellular Carcinoma Progression by Negative Regulation of β-catenin/TCF/LEF Signalling

Hong Gao, Fen-Fen Yin, Dong-Xian Guan, Yu-Xiong Feng, Qian-Wen Zheng, Xiang Wang, Min Zhu, Xue-Li Zhang, Shu-Qun Cheng, Tian-Wei Chen, Hao Jiang, Er-Bin Zhang, Jing-Jing Wang, Qian-Zhi Ni, Yan-Mei Yuan, etc.

Cell Prolif. 2019 May;52(3):e12583.

PMID: 30793395

Abstract:

Objectives:
Wnt1-inducible signalling pathway protein 3 (WISP3/CCN6) belongs to the CCN (CYR61/CTGF/NOV) family of proteins, dysregulation of this family contributed to the tumorigenicity of various tumours. In this study, we need to explore its role in hepatocellular carcinoma that remains largely elusive.
Materials and methods:
The expression of WISP3/CCN6 was analysed by qRT-PCR and Western blotting. Effects of WISP3 on proliferation and metastasis of HCC cells were examined, respectively, by MTT assay and Boyden Chamber. Roles of WISP3 on HCC tumour growth and metastatic ability in vivo were detected in nude mice. Related mechanism study was confirmed by immunofluorescence and Western blotting.
Results:
The expression of WISP3 was significantly downregulated in HCC clinical samples and cell lines, and reversely correlated with the tumour size. Forced expression of WISP3 in HCC cells significantly suppressed cell growth and migration in vitro as well as tumour growth and metastatic seeding in vivo. In contrast, downregulation of WISP3 accelerated cell proliferation and migration, and promoted in vivo metastasis. Further study revealed that WISP3 inhibited the translocation of β-catenin to the nucleus by activating glycogen synthase kinase-3β (GSK3β). Moreover, constitutively active β-catenin blocked the suppressive effects of WISP3 on HCC.
Conclusions:
Our study showed that WISP3 suppressed the progression of HCC by negative regulation of β-catenin/TCF/LEF signalling, providing WISP3 as a potential therapeutic candidate for HCC.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP327036895-A	GSK-3β Inhibitor I - CAS 327036-89-5		327036-89-5	Price

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