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

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.