YAP nuclear translocation facilitates radiation resistance in nasopharyngeal carcinoma cells

Feifei Li; Xinhao Peng; Linlin Zheng; Yiqiang Liu; Qianshi Liu; Biqin Zhang; Ying Shi; Hong Wu; Chuan Xu

doi:10.1016/j.bbrc.2023.05.101

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. Epub 2023 May 26.

Authors

Feifei Li¹, Xinhao Peng², Linlin Zheng², Yiqiang Liu³, Qianshi Liu¹, Biqin Zhang², Ying Shi², Hong Wu⁴, Chuan Xu⁵

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: wuhongzao@126.com.
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: xuchuan100@163.com.

PMID: 37290285
DOI: 10.1016/j.bbrc.2023.05.101

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis
Carcinoma* / pathology
Carcinoma* / radiotherapy
Cell Line, Tumor
Humans
Nasopharyngeal Carcinoma / radiotherapy
Nasopharyngeal Neoplasms* / metabolism
Radiation Tolerance
YAP-Signaling Proteins* / metabolism

Substances

YAP1 protein, human
YAP-Signaling Proteins