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

doi:10.1016/j.cellsig.2015.09.014

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

Cell Signal. 2015 Dec;27(12):2515-23. doi: 10.1016/j.cellsig.2015.09.014. Epub 2015 Sep 26.

Authors

Kaijie Wu¹, Bin Wang¹, Yule Chen¹, Jiancheng Zhou¹, Jun Huang¹, Ke Hui¹, Jin Zeng¹, Jianning Zhu¹, Kai Zhang¹, Lei Li¹, Peng Guo¹, Xinyang Wang¹, Jer-Tsong Hsieh², Dalin He³, Jinhai Fan⁴

Affiliations

¹ Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China.
² Department of Urology, University of Texas Southwestern Medical Center, Dallas 75390, TX, USA.
³ Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China. Electronic address: [email protected].
⁴ Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China. Electronic address: [email protected].

PMID: 26410305
DOI: 10.1016/j.cellsig.2015.09.014

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.

Keywords: Bladder cancer; DAB2IP; P-glycoprotein; Pirarubicin; Tumor recurrence; Twist1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
Animals
Antineoplastic Agents / pharmacology*
Antineoplastic Agents / therapeutic use
Cell Line, Tumor
Cell Survival / drug effects
Down-Regulation
Doxorubicin / analogs & derivatives*
Doxorubicin / pharmacology
Doxorubicin / therapeutic use
Drug Resistance, Neoplasm
Female
Humans
Kaplan-Meier Estimate
Mice, Inbred BALB C
Mice, Nude
Neoplasm Invasiveness
Neoplasm Recurrence, Local / metabolism*
Neoplasm Recurrence, Local / mortality
Neoplasm Recurrence, Local / prevention & control
Nuclear Proteins / metabolism
STAT3 Transcription Factor / metabolism
Signal Transduction
Twist-Related Protein 1 / metabolism
Urinary Bladder Neoplasms / drug therapy
Urinary Bladder Neoplasms / epidemiology*
Urinary Bladder Neoplasms / metabolism*
Urinary Bladder Neoplasms / mortality
Urinary Bladder Neoplasms / pathology
Urothelium / metabolism
Urothelium / pathology
Xenograft Model Antitumor Assays
ras GTPase-Activating Proteins / physiology*

Substances

ATP Binding Cassette Transporter, Subfamily B, Member 1
Antineoplastic Agents
DAB2IP protein, human
Nuclear Proteins
STAT3 Transcription Factor
STAT3 protein, human
TWIST1 protein, human
Twist-Related Protein 1
ras GTPase-Activating Proteins
Doxorubicin
pirarubicin