Translational Research Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Ann Surg Oncol. 2020 Jun;27(6):2090-2101. doi: 10.1245/s10434-019-08043-x. Epub 2019 Nov 20.
Rad51 is a protein which plays a vital role in DNA double-strand break repair and maintenance of telomeres. However, the underlying mechanism for its action in esophageal squamous cell carcinoma (ESCC) remains unclear.
Eighty-seven patients with ESCC were enrolled in this study. Expression of Rad51 in ESCC was determined by immunohistochemistry and correlated with clinicopathological variables by Chi square test. The role of Rad51 in patient survival was determined by Kaplan-Meier estimates. The effects of Rad51 knockdown and overexpression on esophageal cancer growth, migration, and invasion were examined using TE8, CE81T, and KYSE70 cells. The mechanisms involved were also analyzed. Nude mice models were used for assessment of tumor growth.
Rad51 staining was predominantly observed in ESCC patients. ESCC patients with high Rad51 expression had significantly decreased survival (P < 0.001) combined with increased tumor size (P = 0.034) and lymph node metastasis (P = 0.039). Rad51 overexpression promoted, while its knockdown attenuated, esophageal cancer cell viability through cell cycle entry and migration/invasion via epithelial-mesenchymal transition. Moreover, Rad51 overexpression increased colony formation in vitro and tumor growth in vivo. In addition, high Rad51 expression increased cancer progression through the p38/Akt/Snail signaling pathway.
This study indicates a new biological role for Rad51 in ESCC progression. Rad51 may serve as a potential prognostic biomarker and therapeutic target for ESCC patients.
Rad51 是一种在 DNA 双链断裂修复和端粒维持中起关键作用的蛋白质。然而，其在食管鳞状细胞癌（ESCC）中的作用机制尚不清楚。
本研究纳入了 87 例 ESCC 患者。通过免疫组织化学检测 ESCC 中 Rad51 的表达，并通过卡方检验与临床病理变量相关。通过 Kaplan-Meier 估计确定 Rad51 对患者生存的作用。使用 TE8、CE81T 和 KYSE70 细胞检测 Rad51 敲低和过表达对食管癌生长、迁移和侵袭的影响，并分析其机制。使用裸鼠模型评估肿瘤生长。
Rad51 染色主要见于 ESCC 患者。Rad51 高表达的 ESCC 患者的生存率显著降低（P<0.001），同时肿瘤体积增大（P=0.034）和淋巴结转移（P=0.039）增加。Rad51 过表达通过细胞周期进入促进，而敲低则通过上皮间质转化抑制食管癌细胞活力、迁移和侵袭。此外，Rad51 过表达增加了体外集落形成和体内肿瘤生长。此外，高 Rad51 表达通过 p38/Akt/Snail 信号通路增加癌症进展。
本研究表明 Rad51 在 ESCC 进展中具有新的生物学作用。Rad51 可作为 ESCC 患者的潜在预后标志物和治疗靶点。
