DAB2 suppresses gastric cancer migration by regulating the Wnt/β-catenin and Hippo-YAP signaling pathways

BACKGROUND: Disabled-2 (DAB2), a potential tumor suppressor, plays an in important role in cancer development and cellular differentiation. Its lower expression levels have founded in many cancers. In addition, DAB2 is involved in multiple signaling pathways, including TGF-β and Wnt signal pathways. Gastric cancer (GC) is a common gastrointestinal malignant tumor. Nonetheless, the role of DAB2 in GC remains unclear. METHODS: Thirty-seven clinical specimens of GC tissues and adjacent non-tumor tissues were examined by immunohistochemistry. Proteins were extracted from two of them to perform Western blot analysis. Then, CMV-MCS-3FLAG-SV40-DAB2 and si-DAB2 were transfected into MGC and SGC cell line, respectively. The migration of GC cells was evaluated by transwell migration assay. And, the expression of migration related proteins was detected by Western blot and immunofluorescence (IF). RESULTS: Eighty-six percent (32/37) of patients DAB2 staining was reduced in GC tissues compared to adjacent normal tissues. Further studies showed that in six human GC cell lines, the level of DAB2 expression was lower than normal gastric epithelial cells, and that DAB2 was closely related to cell migration in vitro. In DAB2 silenced cells, the Wnt/β-catenin signaling was increased and the Hippo-YAP pathway was affected. In addition, lower DAB2 level led to nuclear translocation of β-catenin and Yap. CONCLUSIONS: The lower expression of DAB2 regulates cell migration in GC via interfering with the Wnt and Hippo signaling pathway. Our findings suggested that DAB2 played an important role in the migration of GC.