Extracellular vesicles (EVs) play a vital role in ovarian carcinoma (OvCa) metastasis, yet the mechanisms regulating EV biogenesis remain unclear. Here, we identify CBX2 as a key driver of omental metastasis, with elevated expression in metastatic lesions and association with poor prognosis. CBX2 promotes tumor cell migration, invasion, and metastasis by enhancing EV secretion and pro-metastatic cargo loading through remodeling lipid rafts, cholesterol-rich membrane microdomains essential for EV formation. Deletion of the intrinsically disordered region abolishes lipid raft remodeling and multivesicular body redistribution, indicating dependence on liquid-liquid phase separation (LLPS). CBX2 also transcriptionally upregulates FLOT1 in an LLPS-dependent manner. Disruption of lipid rafts or inhibition of CBX2 phase separation markedly reduces EV production and metastatic potential. These findings reveal an LLPS-dependent mechanism linking CBX2 to lipid raft-mediated EV biogenesis and OvCa metastasis.
Wu et al. (Mon,) studied this question.