Metabolic reprogramming supports the invasive phenotype in malignant melanoma

摘要: Invasiveness is a hallmark of aggressive cancer like malignant melanoma, and factors involved in acquisition or maintenance an invasive phenotype are attractive targets for therapy. We investigated melanoma modulation induced by the metastasis-promoting microenvironmental protein S100A4, focusing on relationship between enhanced cellular motility, dedifferentiation metabolic changes. In poorly motile, well-differentiated Melmet 5 cells, S100A4 stimulated migration, invasion simultaneously down-regulated differentiation genes modulated expression metabolism genes. Metabolic studies confirmed suppressed mitochondrial respiration activated glycolytic flux indicating switch toward aerobic glycolysis, known as Warburg effect. Reversal dichloracetate apoptosis reduced cell growth, particularly cells. This implies that cells with invasiveness get survival benefit from and, therefore, become more vulnerable to glycolysis inhibition. conclusion, our data indicate transition involves reprogramming oxidation which facilitates Therapeutic strategies targeting may therefore be effective against phenotype.