CD59 is a potential biomarker of esophageal squamous cell carcinoma radioresistance by affecting DNA repair.
CD59 is a potential biomarker of esophageal squamous cell carcinoma radioresistance by affecting DNA repair.
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CD59通过影响DNA修复而成为食管鳞状细胞癌放射抗性的潜在生物标志物
DOI：
10.1038/s41419-018-0895-0
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发表时间：
2018-08-30
影响因子：
9
通讯作者：
Hu W
中科院分区：
文献类型：
--
作者：
Zhou Y;Chu L;Wang Q;Dai W;Zhang X;Chen J;Li L;Ding P;Zhang L;Gu H;Li L;Lv X;Zhang W;Zhou D;Zhang P;Cai G;Zhao K;Hu W
放射治疗是食管癌的重要治疗手段。然而，放射抗性的获得最终导致食管癌复发。CD 59是一种膜结合补体调节蛋白，可通过脂筏中的Src激酶调节信号，从而发挥补体非依赖性作用。然而，CD 59对食管癌对电离辐射反应的影响仍不清楚。在本研究中，我们发现CD 59的表达水平与食管癌细胞系和临床标本的放射抗性呈正相关。CD 59高表达提示食管鳞状细胞癌患者放疗后总生存期（OS）和无病生存期（DFS）较差。CD 59基因表达改变调节食管癌细胞对电离辐射的敏感性CD 59缺乏可加重DNA损伤，阻碍细胞增殖，并诱导G2/M期细胞阻滞和细胞衰老，导致DNA损伤修复能力受损。此外，尽管有电离辐射，CD 59缺乏几乎完全降低了Y 416处Src的磷酸化。Src抑制剂saracatinib使食管癌细胞对辐射敏感。因此，CD 59可能是预测食管鳞癌放射抵抗的一个潜在的生物标志物。
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.
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影响因子：
6.4
作者：
Geoerger, Birgit;Gaspar, Nathalie;Vassal, Gilles
通讯作者：
Vassal, Gilles
DOI：
10.1016/0360-3016(82)90459-x
发表时间：
1982-01-01
影响因子：
7
作者：
BARENDSEN, GW
通讯作者：
BARENDSEN, GW
DOI：
10.1016/0360-3016(91)90320-4
发表时间：
1991-11-01
影响因子：
7
作者：
BEDFORD, JS
通讯作者：
BEDFORD, JS
影响因子：
3.9
作者：
Lawless, Conor;Wang, Chunfang;Passos, Joao F.
通讯作者：
Passos, Joao F.
影响因子：
45.3
作者：
Harvey, JM;Clark, GM;Allred, DC
通讯作者：
Allred, DC