CD59 is a potential biomarker of esophageal squamous cell carcinoma radioresistance by affecting DNA repair.

Abstract

Radiation therapy is an important treatment modality for esophageal cancer. However, acquisition of radioresistance ultimately results in esophageal cancer relapse. CD59, a membrane-bound complement regulatory protein, can transduce signals via a Src kinase in the lipid raft, thus playing a complement-independent role. However, the effect of CD59 on the esophageal cancer response to ionizing radiation remains unclear. In this study, we found that the expression level of CD59 was positively correlated with the radioresistance of esophageal cancer cell lines and clinical specimens. High CD59 expression indicated poor overall survival (OS) and disease-free survival (DFS) in esophageal squamous cell carcinoma (ESCC) patients who received radiotherapy. Genetic alteration of CD59 expression modulated the radiosensitivity of esophageal cancer cells to ionizing radiation. CD59 deficiency exacerbated DNA damage, hindered cell proliferation, and induced G2/M cell cycle arrest and cellular senescence, leading to an impaired DNA damage repair ability. In addition, CD59 deficiency almost completely reduced the phosphorylation of Src at Y416 despite ionizing radiation. A Src inhibitor saracatinib sensitized esophageal cancer cells to irradiation. Therefore, CD59 may be a potential biomarker for predicting the radioresistance of ESCC to radiotherapy.

• Authors: Yuzhen Zhou, Li Chu, Qi Wang, Weixing Dai, Xiaozhou Zhang, Jianfeng Chen, Ling Li, Peipei Ding, Long Zhang, Hongyu Gu, Luying Li, Xinyue Lv, Wei Zhang, Danlei Zhou, Pingzhao Zhang, Guoxiang Cai, Kuaile Zhao, Weiguo Hu
• Journal: Cell death & disease (Cell Death Dis) Vol. 9 Issue 9 Pg. 887 (08 30 2018) ISSN: 2041-4889 [Electronic] England
• PMID: 30166523 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Benzodioxoles
• Biomarkers, Tumor
• CD59 Antigens
• Quinazolines
• CD59 protein, human
• saracatinib

Topics

• Animals
• Benzodioxoles (pharmacology)
• Biomarkers, Tumor (genetics)
• CD59 Antigens (antagonists & inhibitors, genetics)
• Cell Line, Tumor
• Cell Proliferation (genetics)
• Cellular Senescence (genetics)
• DNA Damage (genetics)
• DNA Repair (genetics)
• Disease-Free Survival
• Esophageal Neoplasms (genetics, radiotherapy)
• Esophageal Squamous Cell Carcinoma (genetics, radiotherapy)
• G2 Phase Cell Cycle Checkpoints (genetics)
• Humans
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Neoplasm Transplantation
• Quinazolines (pharmacology)
• Radiation Tolerance (genetics)
• Transplantation, Heterologous