Uveal melanoma (UM), the most common primary intraocular
cancer in adults, is among the
tumors with poorer prognosis. Recently, the role of the oncometabolite
lactate has become attractive due to its role as hydroxycarboxylic
acid receptor 1 (HCAR1) activator, as an epigenetic modulator inducing
lysine residues lactylation and, of course, as a glycolysis end-product, bridging the gap between glycolysis and oxidative phosphorylation. The aim of the present study was to dissect in UM cell line (92.1) the role of
lactate as either a metabolite or a signaling molecule, using the known modulators of HCAR1 and of
lactate transporters. Our results show that
lactate (20 mM) resulted in a significant decrease in cell proliferation and migration, acting and switching cell metabolism toward oxidative phosphorylation. These results were coupled with increased
euchromatin content and quiescence in UM cells. We further showed, in a clinical setting, that an increase in
lactate transporters MCT4 and HCAR1 is associated with a spindle-shape histological type in UM. In conclusion, our results suggest that
lactate metabolism may serve as a prognostic marker of UM progression and may be exploited as a potential therapeutic target.