Original Article Low expression of Dapper1 induces malignancy via the Wnt signalling pathway and is associated with poor prognosis in gastric cancer

* Equal contributors. Received November 5, 2015; Accepted January 1, 2016; Epub February 1, 2016; Published February 15, 2016 Abstract: Gastric cancer is the second leading cause of cancer death and remains a major clinical challenge due to poor prognosis and limited treatment options. The Wnt signalling pathway is abnormally activated in gastric cancer as well as many other malignancies. The aim of this study was to explore the clinical significance and prognostic value of Dapper1 expression and its regulation of the Wnt signalling pathway in gastric cancer. Real-time PCR and immunohistochemistry were respectively performed to investigate the expression of DAPPER1 at mRNA and pro- tein level in both gastric cancer tissues and adjacent normal mucosa tissues. We found that DAPPER1 mRNA and protein was commonly downregulated is gastric cancer tissues. The lower expression of DAPPER1 was significantly correlated with tumor invasion, lymph-node metastasis, and TNM stage (P < 0.05). Survival analysis revealed that DAPPER1 is a prognostic predictor of gastric cancer (P = 0.046). Overexpression of DAPPER1 in SGC7901 cells significantly inhibited cell proliferation while increasing apoptosis. Overexpression of DAPPER1 led to reduced ex - pression of Dvl-2, β-catenin, survivin, and bcl-xl. Similarly, there was reduced expression of survivin, the canonical Wnt-signalling target gene. Finally, overexpressed DAPPER1 inhibited tumour growth of SGC7901 cells transplanted into athymic nude mice. In conclusion, our results suggest that downregulation of Dapper1 gene expression in hu- man gastric carcinoma promotes tumour development through regulating the canonical Wnt-signalling pathway.