The Expression of Riboflavin Transporters in Human Cancer

Riboflavin (Rf), otherwise known as vitamin B2, is an essential dietary component and represents the precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), that are important enzymatic cofactors required for carbohydrate, amino acid and lipid metabolism, and other cellular regulatory roles. Humans, being unable to synthesize riboflavin, must obtain it from food, in particular from milk, meats, fatty fish and green vegetables, and, to a lesser amount, from intestinal microflora. After intestinal absorption, Rf is distributed from the blood to several tissues: Rf cellular uptake occurs via specialized carrier-mediated processes supported by three specific members of the solute carrier family 52 (SLC52A), identified and named Rf transporter 1 (RFVT1; SLC52A1), 2(RFVT2;SLC52A2), and 3(RFVT3; SLC52A3), respectively [1, 2]. Once inside the cells, Rf is phosphorylated to FMN by riboflavin kinase (E.C. 2.7.1.26) and it is subsequently metabolized to FAD by FAD synthase (E.C. 2.7.7.2), existing in different isoforms localised in cytosol, mitochondrion and nucleus [3]. A low intake of dietary Rf can lead to negative health consequences, that include the development of colorectal cancer (CRC). We have recently demonstrated that alterations of transcription/translation of RFVTs, lead colon cancer cells to become greedy for the vitamin [4]. The aim of the present study was to investigate whether the expression levels of RFVTs are also altered in uterus and breast cancers. To do this, we used both cell models and human biopsies. We correlated altered expression of translocators with the increase of Rf-derived cofactor levels. The biochemical consequences of altering cellular flavoproteome will be discussed.