Silencing of WISP3 suppresses gastric cancer cell proliferation and metastasis and inhibits Wnt/β-catenin signaling

International Journal of Clinical and Experimental Pathology

Rong-Kun Li¹  Zhi-Gang Zhang¹  Xiao-Mei Yang¹  Fan-Zhi Kong¹  Wen-Ming Zhang¹  Wen-Yi Zhao¹  Shu-Heng Jiang¹  Chun Zhuang¹  Jun Li¹  Hui Cao¹  Jun-Ping Ao¹  Ping He¹  Wen-Xin Qin¹  Lin Tu¹  Fang Fang¹ 

关键词: WISP3;    gastric cancer cell;    proliferation;    invasion;    canonical Wnt signaling;   

DOI  :  

学科分类：生理学与病理学

来源: e-Century Publishing Corporation

【 摘 要 】

CCN6/Wnt1-inducible signaling protein-3 (CCN6/WISP3) is a cysteine-rich protein that belongs to the CCN (Cyr61, CTGF, Nov) family of matricellular proteins, which are often dysregulated in cancers. However, the functional role and clinical significance of WISP3 in gastric cancer remain unclear. In this study, we found that silencing of WISP3 suppressed gastric cancer cell proliferation, migration and invasion. Cell adhesion to collagens (collagen I and IV), but not to fibronectin, were significantly inhibited by silencing of WISP3. Furthermore, silencing of WISP3 prevented β-catenin transferring from cell cytoplasm to nuclear, and suppressed canonical Wnt/β-catenin signaling and its downstream target genes, cyclin D1 and TCF-4. By immunohistochemical analysis of 379 patients, we found that the expression of WISP3 is closely associated with gastric cancer size and tumor invasion, and indicates a poor prognosis in both test cohort (253 patients) and validation cohort (126 patients). Moreover, the expression of WISP3 was positively correlated with the expression of cyclin D1 and TCF-4 in gastric cancer tissues. Taken together, our data suggests that WISP3 might be a promising prognostic factor and WISP3-Wnt/β-catenin axis may be a new therapeutic target for the intervention of gastric cancer growth and metastasis.

【 授权许可】

Unknown