Downregulation of DAB2IP results in cell proliferation and invasion and contributes to unfavorable outcomes in bladder cancer.
Downregulation of DAB2IP results in cell proliferation and invasion and contributes to unfavorable outcomes in bladder cancer.
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DAB2IP 的下调会导致细胞增殖和侵袭，并导致膀胱癌的不良结果
DOI：
10.1111/cas.12407
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发表时间：
2014-06
期刊：
影响因子：
5.7
通讯作者：
Ye DW
中科院分区：
文献类型：
--
作者：
Shen YJ;Kong ZL;Wan FN;Wang HK;Bian XJ;Gan HL;Wang CF;Ye DW
DOC-2/DAB 2相互作用蛋白（DAB 2 IP）是Ras GTP酶激活蛋白家族的成员。它已被证明是经常下调，在几个人类恶性肿瘤的预后不良的因素。本研究分析了135例膀胱尿路上皮癌（UCB）患者行根治性膀胱切除术加双侧淋巴结清扫术后的临床病理特征和结果，并采用MTT法、集落形成实验、细胞周期实验、细胞迁移和侵袭实验评价了DAB 2 IP表达下调对UCB的影响。DAB 2 IP的低表达与高病理分期（P = 0.002）、高病理分级（P = 0.02）、肿瘤大小> 3cm（P = 0.04）和存在组织学变异（P = 0.01）显著相关。DAB 2 IP是疾病复发（风险比，2.67; P = 0.034）和癌症特异性生存（风险比，2.79; P = 0.038）的独立预后因素。DAB 2 IP的敲低可促进细胞增殖、迁移和侵袭。DAB 2 IP的下调可激活ERK和Akt通路，并与上皮-间质转化标志物如E-cadherin和vimentin的表达相关。总之，DAB 2 IP的下调与生物学侵袭性UCB的特征相关，并导致细胞增殖、迁移和膀胱癌的侵袭。DAB 2 IP可能作为UCB患者根治性膀胱切除术和双侧淋巴结清扫术治疗的一个有前途的生物标志物。
The DOC-2/DAB2 interactive protein (DAB2IP) is a member of the Ras GTPase-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 DAB2IP 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 DAB2IP knockdown in vitro using the MTT method, colony formation assay, cell cycle assay, and cell migration and invasive assay. We found low expression of DAB2IP 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). DAB2IP 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 DAB2IP could promote cell proliferation, migration, and invasion. Downregulation of DAB2IP 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 DAB2IP is associated with features of biologically aggressive UCB and results in cell proliferation, migration, and invasion of bladder cancer. DAB2IP may serve as a promising biomarker in patients with UCB treated by radical cystectomy and bilateral lymph node dissection.
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影响因子：
4.5
作者：
Tilki, Derya;Shariat, Shahrokh F.;Gupta, Amit
通讯作者：
Gupta, Amit
DOI：
10.1073/pnas.0908458106
发表时间：
2009-11-24
影响因子：
11.1
作者：
Xie, Daxing;Gore, Crystal;Hsieh, Jer-Tsong
通讯作者：
Hsieh, Jer-Tsong
影响因子：
4.8
作者：
Wang, Z;Tseng, CP;Hsieh, JT
通讯作者：
Hsieh, JT
影响因子：
4.8
作者：
Zhang, HF;Zhang, R;Min, W
通讯作者：
Min, W
影响因子：
4.8
作者：
Chen, H;Toyooka, S;Hsieh, JT
通讯作者：
Hsieh, JT