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

Kaijie Wu, Bin Wang, Yule Chen, Jiancheng Zhou, Jun Huang, Ke Hui, Jin Zeng, Jianning Zhu, Kai Zhang, Lei Li, Peng Guo, Xinyang Wang, Jer Tsong Hsieh, Dalin He, Jinhai Fan

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2515-2523
Number of pages9
JournalCellular Signalling
Volume27
Issue number12
DOIs
StatePublished - Dec 1 2015

Keywords

  • Bladder cancer
  • DAB2IP
  • P-glycoprotein
  • Pirarubicin
  • Tumor recurrence
  • Twist1

ASJC Scopus subject areas

  • Cell Biology

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