IGF2BP2 promotes malignant progression of ovarian cancer by regulating protein synthesis through liquid-liquid phase...

Ovarian cancer (OC) is the most lethal gynecological malignancy, and high expression of IGF2BP2 is significantly associated with poor prognosis. Intracellular macromolecules regulate diverse biological functions via liquid-liquid phase separation (LLPS). However, whether IGF2BP2 undergoes LLPS and promotes tumor progression in OC through spatiotemporal coordination remains elusive. Here, we demonstrate that IGF2BP2 forms condensates through LLPS in OC cells, which recruit target RNAs and translation initiation factors to enhance de novo protein synthesis. Both N6-methyladenosine (m⁶A)-modified RNA binding and acetylation of IGF2BP2 promote its LLPS. However, substitution of five lysines and one glycine with glutamine within the m⁶A-binding pocket of IGF2BP2 blocks acetylation and disrupts its LLPS, which in turn dampens global protein synthesis and abolishes the oncogenic activity of IGF2BP2 in OC. Our findings reveal that IGF2BP2-driven LLPS promotes OC progression by enhancing protein synthesis, highlighting its potential as a therapeutic target.