Two-faced activity of RNF8: What twists it from a genome guardian to a cancer facilitator?

The RING finger protein 8 (RNF8)-induced ubiquitination signaling cascade promotes DNA repair and maintains genomic stability. Our study reveals an unexpected action of RNF8 in promoting cancer metastasis, cancer stem cell formation, and chemoresistance through the regulation of TWIST lysine 63 (K63)-linked ubiquitination, suggesting that RNF8 may serve as a new cancer prognosis marker and therapeutic target.