title: Twisted epithelial-to-mesenchymal transition promotes progression of surviving bladder cancer T24 cells with hTERT-dysfunction.
abstract: BACKGROUND
  Human cancer cells maintain telomeres to protect cells from senescence through telomerase activity (TA) or alternative lengthening of telomeres (ALT) in different cell types. Moreover, cellular senescence can be bypassed by Epithelial-to-mesenchymal transition (EMT) during cancer progression in diverse solid tumors. However, it has not been elucidated the characteristics of telomere maintenance and progression ability after long-term culture in bladder cancer T24 cells with hTERT dysfunction.
  
  
  RESULTS
  In this study, by using a dominant negative mutant human telomerase reverse transcriptase (hTERT) vector to inhibit TA in bladder cancer T24 cells, we observed the appearance of long phenotype of telomere length and the ALT-associated PML body (APB) complex after the 27(th) passage, indicating the occurrence of ALT-like pathway in surviving T24/DN868A cells with telomerase inhibition. Meanwhile, telomerase inhibition resulted in significant EMT as shown by change in cellular morphology concomitant with variation of EMT markers. Consistently, the surviving T24/DN868A cells showed increased progression ability in vitro and in vivo. In addition, we found Twist was activated to mediate EMT in surviving T24/DN868A samples.
  
  
  CONCLUSIONS
  Taken together, our findings indicate that bladder cancer T24 cells may undergo the telomerase-to-ALT-like conversion and promote cancer progression at advanced stages through promoting EMT, thus providing novel possible insight into the mechanism of resistance to telomerase inhibitors in cancer treatment.
authors: Department of Urology, First Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi, China.
authors: Yan
authors: Y
authors: Xue
authors: Lei
authors: L
authors: Li
authors: Dong
authors: D
authors: Zhang
authors: Kaijie
authors: K
authors: Wu
authors: Yule
authors: Y
authors: Chen
authors: Jin
authors: J
authors: Zeng
authors: Xinyang
authors: X
authors: Wang
authors: Dalin
authors: D
authors: He
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002999:Clone Cells / Q000187:drug effects / Q000473:pathology; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D004791:Enzyme Inhibitors / Q000494:pharmacology; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D005799:Genes, Dominant / Q000235:genetics; D006801:Humans; D051379:Mice; D009154:Mutation; D009361:Neoplasm Invasiveness; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D016615:Telomere / Q000378:metabolism; D059505:Telomere Homeostasis / Q000187:drug effects / Q000235:genetics; D051879:Twist-Related Protein 1 / Q000378:metabolism*; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000473:pathology*
chemical_list: D004791:Enzyme Inhibitors; D051879:Twist-Related Protein 1; C509186:TERT protein, human; D019098:Telomerase