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The  DOC ‐2/ DAB 2 interactive protein ( DAB 2 IP ) is a member of the Ras  GTP ase‐activating protein family. It has been shown to be often downregulated and a poor prognostic factor in several human malignancies. In this study, we analyzed the clinicopathological features and outcomes of  DAB 2 IP  expression in 135 patients with urothelial carcinoma of the bladder ( UCB ) treated by radical cystectomy plus bilateral lymph node dissection, and evaluated the effect of  DAB 2 IP  knockdown  in vitro  using the  MTT  method, colony formation assay, cell cycle assay, and cell migration and invasive assay. We found low expression of  DAB 2 IP  was significantly associated with high pathological stage ( P  = 0.002), high pathological grade ( P  = 0.02), tumor size more than 3 cm ( P  = 0.04), and presence of histological variants ( P  = 0.01).  DAB 2 IP  was an independent prognostic factor of disease recurrence (hazard ratio, 2.67;  P  = 0.034) and cancer‐specific survival (hazard ratio, 2.79;  P  = 0.038). Knockdown of  DAB 2 IP  could promote cell proliferation, migration, and invasion. Downregulation of  DAB 2 IP  could activate the  ERK  and Akt pathways and was correlated with the expression of epithelial–mesenchymal transition markers, such as E‐cadherin and vimentin. In conclusion, downregulation of  DAB 2 IP  is associated with features of biologically aggressive  UCB  and results in cell proliferation, migration, and invasion of bladder cancer.  DAB 2 IP  may serve as a promising biomarker in patients with  UCB  treated by radical cystectomy and bilateral lymph node dissection.

Downregulation of DAB 2 IP results in cell proliferation and invasion and contributes to unfavorable outcomes in bladder cancer