MRE11 promotes oral cancer progression through RUNX2/CXCR4/AKT/FOXA2 signaling in a nuclease-independent manner

Wang, Y.-Y. et al. (2021) MRE11 promotes oral cancer progression through RUNX2/CXCR4/AKT/FOXA2 signaling in a nuclease-independent manner. Oncogene, 40(20), pp. 3510-3532. (doi: 10.1038/s41388-021-01698-5) (PMID:33927349) (PMCID:PMC8134045)

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Abstract

MRE11, the nuclease component of RAD50/MRE11/NBS1 DNA repair complex which is essential for repair of DNA double-strand-breaks in normal cells, has recently garnered attention as a critical factor in solid tumor development. Herein we report the crucial role of MRE11 in oral cancer progression in a nuclease-independent manner and delineate its key downstream effectors including CXCR4. MRE11 expression in oral cancer samples was positively associated with tumor size, cancer stage and lymph node metastasis, and was predictive of poorer patient survival and radiotherapy resistance. MRE11 promoted cell proliferation/migration/invasion in a nuclease-independent manner but enhanced radioresistance via a nuclease-dependent pathway. The nuclease independent promotion of EMT and metastasis was mediated by RUNX2, CXCR4, AKT, and FOXA2, while CXCR4 neutralizing antibody mitigated these effects in vitro and in vivo. Collectively, MRE11 may serve as a crucial prognostic factor and therapeutic target in oral cancer, displaying dual nuclease dependent and independent roles that permit separate targeting of tumor vulnerabilities in oral cancer treatment.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Hsieh, Dr Ya-Ching and Lo, Mr Steven
Authors: Wang, Y.-Y., Chen, Y.-K., Lo, S., Chi, T.-C., Chen, Y.-H., Hu, S. C.-S., Chen, Y.-W., Jiang, S. S., Tsai, F.-Y., Liu, W., Li, R.-N., Hsieh, Y.-C., Huang, C.-J., and Yuan, S.-S. F.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
Journal Name:Oncogene
Publisher:Nature Research
ISSN:0950-9232
ISSN (Online):1476-5594
Published Online:29 April 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Oncogene 40(2): 3510-3532
Publisher Policy:Reproduced under a Creative Commons licence

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