DAB2IP regulates the chemoresistance to pirarubicin and tumor recurrence of non-muscle invasive bladder cancer through STAT3/Twist1/P-glycoprotein signaling

被引：46

作者：

Wu, Kaijie ^{[1
]}

Wang, Bin ^{[1
]}

Chen, Yule ^{[1
]}

Zhou, Jiancheng ^{[1
]}

Huang, Jun ^{[1
]}

Hui, Ke ^{[1
]}

Zeng, Jin ^{[1
]}

Zhu, Jianning ^{[1
]}

Zhang, Kai ^{[1
]}

Li, Lei ^{[1
]}

Guo, Peng ^{[1
]}

Wang, Xinyang ^{[1
]}

Hsieh, Jer-Tsong ^{[2
]}

He, Dalin ^{[1
]}

Fan, Jinhai ^{[1
]}

机构：

[1] Xi An Jiao Tong Univ, Affiliated Hosp 1, Dept Urol, Xian 710061, Peoples R China

[2] Univ Texas SW Med Ctr Dallas, Dept Urol, Dallas, TX 75390 USA

来源：

CELLULAR SIGNALLING | 2015年 / 27卷 / 12期

基金：

中国国家自然科学基金;

关键词：

Bladder cancer; Pirarubicin; Tumor recurrence; DAB2IP; Twist1; P-glycoprotein; ABERRANT PROMOTER METHYLATION; PROTEIN HDAB2IP GENE; PROSTATE-CANCER; MESENCHYMAL TRANSITION; CELL CARCINOMAS; DOWN-REGULATION; EXPRESSION; RESISTANCE; GROWTH; PROLIFERATION;

D O I：

10.1016/j.cellsig.2015.09.014

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

There is a high frequency of tumor recurrence in non-muscle invasive bladder cancer (NMIBC) after transurethral resection and postoperative intravesical chemotherapy, however, the molecular mechanisms leading to the chemoresistance and tumor re-growth remain largely unknown. In this study, we observed a significant decrease of DAB2IP expression in high-grade and recurrent NMIBC specimens, which was negatively correlated with Twist1 expression and predicted a lower recurrence-free survival of patients. Mechanistically, DAB2IP could inhibit the phosphorylation and transactivation of STAT3, and then subsequently suppress the expression of Twist1 and its target gene P-glycoprotein, both of which were crucial for the pirarubicin chemoresistance and tumor re-growth of bladder cancer cells. Overall, this study reveals a new promising biomarker modulating the chemoresistance and tumor recurrence of NMIBC after bladder preservation surgery. (C) 2015 Elsevier Inc. All rights reserved.

引用

页码：2515 / 2523

页数：9

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