2. Academic Validation
  3. Lactate Rewrites the Metabolic Reprogramming of Uveal Melanoma Cells and Induces Quiescence Phenotype

Lactate Rewrites the Metabolic Reprogramming of Uveal Melanoma Cells and Induces Quiescence Phenotype

  • Int J Mol Sci. 2022 Dec 20;24(1):24. doi: 10.3390/ijms24010024.
Lucia Longhitano 1,  Sebastiano Giallongo 1,  Laura Orlando 1,  Giuseppe Broggi 2,  Antonio Longo 3,  Andrea Russo 3,  Rosario Caltabiano 2,  Cesarina Giallongo 2,  Ignazio Barbagallo 1,  Michelino Di Rosa 1,  Rosario Giuffrida 1,  Rosalba Parenti 1,  Giovanni Li Volti 1,  Nunzio Vicario 1,  Daniele Tibullo 1
Affiliations

Affiliations

  • 1 Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy.
  • 2 Department of Medical, Surgical Sciences and Advanced Technologies "G.F. Ingrassia", Anatomic Pathology, University of Catania, 95123 Catania, Italy.
  • 3 Department of Ophthalmology, University of Catania, 95123 Catania, Italy.
PMID: 36613471 DOI: 10.3390/ijms24010024
Abstract

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.

Keywords

HCAR1; lactate; lactylation; metabolism; uveal melanoma.

Figures
Products