Telomere-Binding Protein TPP1 Modulates Telomere Homeostasis and Confers Radioresistance to Human Colorectal Cancer Cells |
| |
| Authors: | Lei Yang Wenbo Wang Liu Hu Xiaoxi Yang Juan Zhong Zheng Li Hui Yang Han Lei Haijun Yu ZhengKai Liao Fuxiang Zhou Conghua Xie Yunfeng Zhou |
| |
| Institution: | 1. Hubei Cancer Clinical Study Center, Hubei Key Laboratory of Tumor Biological Behaviors, Zhongnan Hospital, Wuhan University, Wuhan, China.; 2. Department of Radiation Oncology & Medical Oncology, Zhongnan Hospital, Wuhan University, Wuhan, China.; 3. Department of Oncology, the Fifth Hospital of Wuhan, Wuhan, China.; Texas Tech University Health Sciences Center, United States of America, |
| |
| Abstract: | BackgroundRadiotherapy 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.Principal FindingsIn 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.ConclusionsWe 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. |
| |
| Keywords: | |
|
|
