國家衛生研究院 NHRI:Item 3990099045/13408
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    题名: MRE11 promotes oral cancer progression through RUNX2/CXCR4/AKT/FOXA2 signaling in a nuclease-independent manner
    作者: Wang, YY;Chen, YK;Lo, S;Chi, TC;Chen, YH;Hu, SC;Chen, YW;Jiang, SS;Tsai, FY;Liu, W;Li, RN;Hsieh, YC;Huang, CJ;Yuan, SS
    贡献者: National Institute of Cancer Research
    摘要: 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.
    日期: 2021-05
    關聯: Oncogene. 2021 May;40(20):3510-3532.
    Link to: http://dx.doi.org/10.1038/s41388-021-01698-5
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0950-9232&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000645517200002
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85105185584
    显示于类别:[江士昇] 期刊論文
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