The DNA Damage Transducer RNF8 Facilitates Cancer Chemoresistance and Progression through Twist Activation.

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 c

SUBMITTER: Lee HJ 

PROVIDER: S-EPMC5026628 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature