Open AccessDownregulation of DAB 2 IP results in cell proliferation and invasion and contributes to unfavorable outcomes in bladder cancer
Author(s) -
Shen YiJun,
Kong ZhaoLu,
Wan FangNing,
Wang HongKai,
Bian XiaoJie,
Gan HuaLei,
Wang ChaoFu,
Ye DingWei
Publication year - 2014
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12407
Subject(s) - downregulation and upregulation , cancer research , cystectomy , bladder cancer , gene knockdown , cell growth , urothelial cell , protein kinase b , gentamicin protection assay , medicine , cancer , metastasis , chemistry , biology , apoptosis , signal transduction , microbiology and biotechnology , biochemistry , gene
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.