PUBLICATION
MRE11 promotes oral cancer progression through RUNX2/CXCR4/AKT/FOXA2 signaling in a nuclease-independent manner
- Authors
- Wang, Y.Y., Chen, Y.K., Lo, S., Chi, T.C., Chen, Y.H., Hu, S.C., Chen, Y.W., Jiang, S.S., Tsai, F.Y., Liu, W., Li, R.N., Hsieh, Y.C., Huang, C.J., Yuan, S.F.
- ID
- ZDB-PUB-220115-8
- Date
- 2021
- Source
- Oncogene 40: 3510-3532 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Line, Tumor
- Cell Movement/physiology
- Cell Proliferation/physiology
- Core Binding Factor Alpha 1 Subunit/metabolism*
- DNA Repair Enzymes/metabolism*
- Deoxyribonucleases/metabolism*
- Female
- Hepatocyte Nuclear Factor 3-beta/metabolism*
- Heterografts
- Humans
- MRE11 Homologue Protein/genetics
- MRE11 Homologue Protein/metabolism*
- Male
- Mice
- Mice, Inbred NOD
- Mice, SCID
- Mouth Neoplasms/genetics
- Mouth Neoplasms/metabolism*
- Mouth Neoplasms/pathology
- Mouth Neoplasms/radiotherapy
- Prognosis
- Proto-Oncogene Proteins c-akt/metabolism
- Radiation Tolerance
- Receptors, CXCR4/metabolism*
- Signal Transduction
- Survival Rate
- Zebrafish
- PubMed
- 33927349 Full text @ Oncogene
Citation
Wang, Y.Y., Chen, Y.K., Lo, S., Chi, T.C., Chen, Y.H., Hu, S.C., Chen, Y.W., Jiang, S.S., Tsai, F.Y., Liu, W., Li, R.N., Hsieh, Y.C., Huang, C.J., Yuan, S.F. (2021) MRE11 promotes oral cancer progression through RUNX2/CXCR4/AKT/FOXA2 signaling in a nuclease-independent manner. Oncogene. 40:3510-3532.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping