YAP nuclear translocation facilitates radiation resistance in nasopharyngeal carcinoma cells PMID: 37290285

ADC Targets in Oncology

2026-04-10

YAP nuclear translocation facilitates radiation resistance in nasopharyngeal carcinoma cells

Biochem Biophys Res Commun. 2023 Aug 30:670:109-116. doi: 10.1016/j.bbrc.2023.05.101.

Feifei Li ¹ , Xinhao Peng ² , Linlin Zheng ² , Yiqiang Liu ³ , Qianshi Liu ¹ , Biqin Zhang ² , Ying Shi ² , Hong Wu ⁴ , Chuan Xu ⁵

Affiliations

1. 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.
2. School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, 610047, China.
3. 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.
4. 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. Electronic address: [email protected].
5. 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. Electronic address: [email protected].

Abstract

Objectives: Investigate the role of the Hippo-YAP signaling pathway in radioresistant Nasopharyngeal Carcinoma (NPC).

Methods: 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.

Results: 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.

Conclusions: 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.