👤 Claudio Brancolini

Nerve-Glial Antigen 2/Chondroitin Sulphate Proteoglycan 4 (NG2/CSPG4) is the largest membrane-intercalated cell surface component of the human proteome known to date. NG2/CSPG4 is endowed with the capability of engaging a myriad of molecular interactions and exert co-receptor functions, of which primary ones are sequestering of growth factors and the anchoring of cells to the extracellular matrix. However, the nature of the interactive dynamics of the proteoglycan remains veiled because of its conspicuous size and structural complexity. By leveraging on a multi-scale Show less

Metabolic adaptations are emerging as common traits of cancer cells and tumor progression. In vitro transformation of NIH 3T3 cells allows the analysis of the metabolic changes triggered by a single oncogene. In this work, we have compared the metabolic changes induced by H-RAS and by the nuclear resident mutant of histone deacetylase 4 (HDAC4). RAS-transformed cells exhibit a dominant aerobic glycolytic phenotype characterized by up-regulation of glycolytic enzymes, reduced oxygen consumption and a defect in complex I activity. In this model of transformation, glycolysis is strictly required for sustaining the ATP levels and the robust cellular proliferation. By contrast, in HDAC4/TM transformed cells, glycolysis is only modestly up-regulated, lactate secretion is not augmented and, instead, mitochondrial oxygen consumption is increased. Our results demonstrate that cellular transformation can be accomplished through different metabolic adaptations and HDAC4/TM cells can represent a useful model to investigate oncogene-driven metabolic changes besides the Warburg effect. Show less