title: Telomere-binding protein TPP1 modulates telomere homeostasis and confers radioresistance to human colorectal cancer cells.
abstract: BACKGROUND
  Radiotherapy is one of the major therapeutic strategies in cancer treatment. The telomere-binding protein TPP1 is an important component of the shelterin complex at mammalian telomeres. Our previous reports showed that TPP1 expression was elevated in radioresistant cells, but the exact effects and mechanisms of TPP1 on radiosensitivity is unclear.
  
  
  RESULTS
  In this study, we found that elevated TPP1 expression significantly correlated with radioresistance and longer telomere length in human colorectal cancer cell lines. Moreover, TPP1 overexpression showed lengthened telomere length and a significant decrease of radiosensitivity to X-rays. TPP1 mediated radioresistance was correlated with a decreased apoptosis rate after IR exposure. Furthermore, TPP1 overexpression showed prolonged G2/M arrest mediated by ATM/ATR-Chk1 signal pathway after IR exposure. Moreover, TPP1 overexpression accelerated the repair kinetics of total DNA damage and telomere dysfunction induced by ionizing radiation.
  
  
  CONCLUSIONS
  We demonstrated that elevated expressions of TPP1 in human colorectal cancer cells could protect telomere from DNA damage and confer radioresistance. These results suggested that TPP1 may be a potential target in the radiotherapy of colorectal cancer.
authors.affiliation: Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, Wuhan, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.forename: Wenbo
authors.initials: W
authors.lastname: Wang
authors.forename: Liu
authors.initials: L
authors.lastname: Hu
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Yang
authors.forename: Juan
authors.initials: J
authors.lastname: Zhong
authors.forename: Zheng
authors.initials: Z
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.forename: Han
authors.initials: H
authors.lastname: Lei
authors.forename: Haijun
authors.initials: H
authors.lastname: Yu
authors.forename: ZhengKai
authors.initials: Z
authors.lastname: Liao
authors.forename: Fuxiang
authors.initials: F
authors.lastname: Zhou
authors.forename: Conghua
authors.initials: C
authors.lastname: Xie
authors.forename: Yunfeng
authors.initials: Y
authors.lastname: Zhou
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D000071877:Checkpoint Kinase 1; D004249:DNA Damage; D004260:DNA Repair / Q000235:genetics*; D004273:DNA, Neoplasm / Q000378:metabolism*; D059565:G2 Phase Cell Cycle Checkpoints / Q000528:radiation effects; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011836:Radiation Tolerance / Q000235:genetics*; D000089804:Shelterin Complex; D015398:Signal Transduction; D016615:Telomere / Q000737:chemistry / Q000378:metabolism* / Q000528:radiation effects; D059505:Telomere Homeostasis / Q000235:genetics; D034501:Telomere-Binding Proteins; D014965:X-Rays
chemical_list: C495876:ACD protein, human; D004273:DNA, Neoplasm; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C000605867:CHEK1 protein, human; D000071877:Checkpoint Kinase 1