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Research Paper|Volume 12, Issue 20|pp 20380—20395

Rab1A promotes cancer metastasis and radioresistance through activating GSK-3β/Wnt/β-catenin signaling in nasopharyngeal carcinoma

Xian-Zi Yang1, Xi-Min Chen1, Li-Si Zeng2, Jin Deng3, Lei Ma1, Chuan Jin1, Ren Wang2,7, Meng-He Wang4, Yue-Feng Wen3,5, Xiao-Liang Wu6, Hui-Yun Wang7, Shu-Zhong Cui8
  • 1Department of Medical Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 510095, China
  • 2Institute of Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 510095, China
  • 3Department of Radiation Oncology, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 510095, China
  • 4Department of Clinical Laboratory, Maternity and Children's Healthcare Hospital of Foshan, Foshan 528000, China
  • 5State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China
  • 6Department of Oncology, Guizhou Provincial People’s Hospital, Guiyang 550200, China
  • 7State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China
  • 8Department of Abdominal Surgery, Affiliated Cancer Hospital and Institute of Guangzhou Medical University, Guangzhou 510095, China
* Equal contribution
Received: March 25, 2020Accepted: July 14, 2020Published: October 17, 2020
https://doi.org/10.18632/aging.103829

Copyright: © 2020 Yang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Many articles have reported that Rab1A was overexpressed in a variety of human cancers and involved in tumor progression and metastasis. However, the biological function and molecular mechanism of Rab1A in nasopharyngeal carcinoma (NPC) remained unknown until now. Here we found that Rab1A overexpression is a common event and was positively associated with distant metastasis and poor prognosis of NPC patients. Functionally, Rab1A depletion inhibited the migration and EMT phenotype of NPC cells, whereas Rab1A overexpression led to the opposite effect. Furthermore, we reveal an important role for Rab1A protein in the induction of radioresistance via regulating homologous recombination (HR) signaling pathway. Mechanistically, Rab1A activated Wnt/β-catenin signaling by inhibiting the activity of GSK-3β via phosphorylation at Ser9. Then Wnt/β-catenin signaling induced NPC cells radioresistance and metastasis through nuclear translocation of β-catenin and transcription upregulation of HR pathway-related and EMT-related genes expression. In general, this study shows that Rab1A may serve as a potential biomarker for predicting prognosis in NPC patients. Targeting Rab1A and Wnt/β-catenin signaling may hold promise to overcome NPC radioresistance.