Disabled homolog-2 (DAB2) has been reported to be a tumor suppressor gene. However, a number of contrary studies suggested that DAB2 promotes
tumor invasion in urothelial
carcinoma of the bladder (UCB). Here, we investigated the clinical role and
biological function of DAB2 in human UCB. Immunohistochemical staining analysis for DAB2 was carried out on UCB tissue specimens. DAB2 expression levels were compared with clinicopathological factors. DAB2 was knocked-down by
small interfering RNA (
siRNA) transfection, and then its effects on cell proliferation, invasion, and migration, and changes to epithelial-mesenchymal transition (EMT)-related
proteins were evaluated. In our in vivo assays,
tumor-bearing athymic nude mice subcutaneously inoculated with human UCB cells (MGH-U-3 or UM-UC-3) were treated by DAB2-targeting
siRNA. Higher expression of DAB2 was associated with higher clinical T category, high
tumor grade, and poor oncological outcome. The knock-down of DAB2 decreased both invasion and migration ability and expression of EMT-related
proteins. Significant inhibitory effects on
tumor growth and invasion were observed in xenograft
tumors of UM-UC-3 treated by DAB2-targeting
siRNA. Our findings suggested that DAB2 expression was associated with poor prognosis through increased oncogenic properties including
tumor proliferation, migration, invasion, and enhancement of EMT in human UCB.