Collaborative Innovation Centre of Regenerative Medicine and Medical BioResource Development and Application Co-constructed by the Province and Ministry, Guangxi Medical University, Nanning, Guangxi, 530021, China; Department of Oncology & Cancer Institute, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610072, China; Department of Laboratory Medicine and Sichuan Provincial Key Laboratory for Human Disease Gene Study, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610072, China.
School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610047, China.
Biochem Biophys Res Commun. 2023 Aug 30;670:109-116. doi: 10.1016/j.bbrc.2023.05.101. Epub 2023 May 26.
Investigate the role of the Hippo-YAP signaling pathway in radioresistant Nasopharyngeal Carcinoma (NPC).
Establishment of radioresistant CNE-1 cells (CNE-1-RR) by gradually increasing ionizing radiation (IR) doses, and identifying the apoptosis of CNE-1-RR by flow cytometry. We employed immunoblot and immunofluorescence staining to detect the expression of YAP in both CNE-1-RR and control group cells. Moreover, we validated the role of YAP in CNE-1-RR by inhibiting its nuclear translocation.
In contrast to the control group, radioresistant NPC cells demonstrated significant YAP dephosphorylation and nuclear translocation. CNE-1-RR cells exhibited enhanced activation of γ-H2AX (Ser139) upon exposure to IR and greater recruitment of double-strand breaks (DSBs) repair-related proteins. Additionally, inhibiting YAP nuclear translocation in radioresistant CNE-1-RR cells significantly increased their sensitivity to radiotherapy.
The present investigation has unveiled the intricate mechanisms and physiological roles of YAP in CNE-1-RR cells exhibiting resistance to IR. Based on our findings, it can be inferred that a combinational therapeutic strategy involving radiotherapy and inhibitors that impede the nuclear translocation of YAP holds promising potential for treating radioresistant NPC.
探讨 Hippo-YAP 信号通路在鼻咽癌（NPC）放射抵抗中的作用。
通过逐渐增加电离辐射（IR）剂量，建立放射抵抗的 CNE-1 细胞（CNE-1-RR），并通过流式细胞术检测 CNE-1-RR 的细胞凋亡。我们采用免疫印迹和免疫荧光染色检测 CNE-1-RR 和对照组细胞中 YAP 的表达。此外，我们通过抑制其核转位来验证 YAP 在 CNE-1-RR 中的作用。
与对照组相比，放射抵抗的 NPC 细胞表现出明显的 YAP 去磷酸化和核转位。CNE-1-RR 细胞在受到 IR 照射后，γ-H2AX（Ser139）的激活显著增强，双链断裂（DSBs）修复相关蛋白的募集增加。此外，抑制放射抵抗的 CNE-1-RR 细胞中 YAP 的核转位显著增加了它们对放射治疗的敏感性。
本研究揭示了 YAP 在具有 IR 抵抗能力的 CNE-1-RR 细胞中的复杂机制和生理作用。基于我们的发现，可以推断出放射治疗联合抑制 YAP 核转位的抑制剂的联合治疗策略可能为治疗放射抵抗性 NPC 提供新的途径。
