title: Twist confers chemoresistance to anthracyclines in bladder cancer through upregulating P-glycoprotein.
abstract: BACKGROUND
  The membrane transporter P-glycoprotein (P-gp) was found to mediate chemoresistance, which is one of the obstacles to effective chemotherapy in several types of human cancer. The transcription factor Twist, which has been reported to participate in cancer invasion and metastasis, also plays a vital role in the progression of chemoresistance. However, the effect of Twist on P-gp-related chemoresistance remains dubious.
  
  
  RESULTS
  We found that Twist can regulate the expression of P-gp and then confer resistance to anthracycline drugs in human bladder cancer cells. Firstly, Twist was found to be coexpressed with P-gp in human bladder cancer cells and tissues, which were associated with enhanced chemoresistance to anthracycline drugs. Secondly, knockdown of Twist by specific siRNA treatment significantly sensitized bladder cancer cells to anthracycline drugs via inhibiting P-gp expression. Bladder cancer cells that survived transient exposure to anthracycline drugs showed higher levels of P-gp expression and more nuclear localization of Twist than untreated cells.
  
  
  CONCLUSIONS
  We report a novel mechanism of anthracycline chemoresistance in bladder cancer in which activated Twist mediates P-gp expression in addition to its antiapoptotic roles. Therapeutic strategies targeting Twist may improve the management of recurrent bladder cancer after chemotherapy.
authors.affiliation: Department of Urology, The First Hospital of Xi'an Jiaotong University, Xi'an, PR China.
authors.forename: Yule
authors.initials: Y
authors.lastname: Chen
authors.forename: Lei
authors.initials: L
authors.lastname: Li
authors.forename: Jin
authors.initials: J
authors.lastname: Zeng
authors.forename: Kaijie
authors.initials: K
authors.lastname: Wu
authors.forename: Jiancheng
authors.initials: J
authors.lastname: Zhou
authors.forename: Peng
authors.initials: P
authors.lastname: Guo
authors.forename: Dong
authors.initials: D
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Xue
authors.forename: Liang
authors.initials: L
authors.lastname: Liang
authors.forename: Xinyang
authors.initials: X
authors.lastname: Wang
authors.forename: Luke S
authors.initials: LS
authors.lastname: Chang
authors.forename: Dalin
authors.initials: D
authors.lastname: He
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018943:Anthracyclines / Q000494:pharmacology* / Q000627:therapeutic use; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051879:Twist-Related Protein 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D034741:RNA, Small Interfering; D051879:Twist-Related Protein 1; D004317:Doxorubicin