國家衛生研究院 NHRI:Item 3990099045/10005
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/10005


    Title: The DNA damage transducer RNF8 facilitates cancer chemoresistance and progression through twist activation
    Authors: Lee, HJ;Li, CF;Ruan, D;Powers, S;Thompson, PA;Frohman, MA;Chan, CH
    Contributors: National Institute of Cancer Research
    Abstract: Twist has been shown to cause treatment failure, cancer progression, and cancer-related death. However, strategies that directly target Twist are not yet conceivable. Here we reveal that K63-linked ubiquitination is a crucial regulatory mechanism for Twist activation. Through an E3 ligase screen and biochemical studies, we unexpectedly identified that RNF8 functions as a direct Twist activator by triggering K63-linked ubiquitination of Twist. RNF8-promoted Twist ubiquitination is required for Twist localization to the nucleus for subsequent EMT and CSC functions, thereby conferring chemoresistance. Our histological analyses showed that RNF8 expression is upregulated and correlated with disease progression, EMT features, and poor patient survival in breast cancer. Moreover, RNF8 regulates cancer cell migration and invasion and cancer metastasis, recapitulating the effect of Twist. Together, our findings reveal a previously unrecognized tumor-promoting function of RNF8 and provide evidence that targeting RNF8 is an appealing strategy to tackle tumor aggressiveness and treatment resistance.
    Date: 2016-09-15
    Relation: Molecular Cell. 2016 Sep 15;63(6):1021-1033.
    Link to: http://dx.doi.org/10.1016/j.molcel.2016.08.009
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1097-2765&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000389514700011
    Cited Times(Scopus): http://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=84991701993
    Appears in Collections:[Others] Periodical Articles

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