RHOA lactylation at oncogenic hotspots promotes oncogenic activity and protein stabilization

RHOA lactylation at K118 (activation) and K162 (stabilization) orchestrated by the PCAF/HDAC3 enzymatic axis, enables constitutive oncogenic signaling to fuel tumor progression. Crucially, we redefine that lactylation at mutation-prone sites functions as a reversible "epi-mutation" system, where metabolic modification dynamically recapitulates oncogenic mutation effects, challenging the genetic/epigenetic dichotomy in oncology and revealing dual targeting of lactylation and canonical RHOA pathways as a potential therapeutic strategy.