Epidermal growth factor up-regulates SLC37A1 gene expression in cancer cells.

An altered metabolism plays a relevant role in tumor proliferation and, particularly, cancer cells often show an enhanced anaerobic glycolysis and a modified lipids metabolism. The SLC37A1 gene product belongs to a family of sugar-phosphate/phosphate exchangers. On the bases of its homology (of about 30%) with the bacterial glycerol-3-phosphate transporter it has been proposed as a possible antiporter for glycerol-3-phosphate (G3P) and inorganic phosphate. G3P represents the starting substrate for the phospholipids biosynthesis that occurs in distinct cellular compartments, e.g. mitochondria, peroxisomes and endoplasmic reticulum. The epidermal growth factor (EGF) is involved in the lipid synthesis enzymes regulation. In this study we demonstrate, for the first time, that the EGF up-regulates SLC37A1 gene transcription and protein translation through the EGFR/MAPK/Fos transduction pathway in cancer cells. These findings should be included in the important stimulatory actions triggered by EGF in tumors. Moreover, immuno-fluorescence studies show the localization of SLC37A1 protein in the endoplasmic reticulum network. All together these data support its role in the lipid synthesis.