title: 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.
authors.affiliation: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Kaijie
authors.initials: K
authors.lastname: Wu
authors.affiliation: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Yule
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Jiancheng
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Ke
authors.initials: K
authors.lastname: Hui
authors.affiliation: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zeng
authors.affiliation: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Jianning
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Guo
authors.affiliation: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China.
authors.forename: Xinyang
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas 75390, TX, USA.
authors.forename: Jer-Tsong
authors.initials: JT
authors.lastname: Hsieh
authors.affiliation: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China. Electronic address: dalinhe@yahoo.com.
authors.forename: Dalin
authors.initials: D
authors.lastname: He
authors.affiliation: Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China. Electronic address: jinhaif029@126.com.
authors.forename: Jinhai
authors.initials: J
authors.lastname: Fan
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000401:mortality / Q000517:prevention & control; D009687:Nuclear Proteins / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D051879:Twist-Related Protein 1 / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000453:epidemiology* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D019459:Urothelium / Q000378:metabolism / Q000473:pathology; D023041:Xenograft Model Antitumor Assays; D020703:ras GTPase-Activating Proteins / Q000502:physiology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; C462952:DAB2IP protein, human; D009687:Nuclear Proteins; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D020703:ras GTPase-Activating Proteins; D004317:Doxorubicin; C027260:pirarubicin
keywords: Bladder cancer; DAB2IP; P-glycoprotein; Pirarubicin; Tumor recurrence; Twist1