Alteration of Riboflavin transporter expression in human cancer

Riboflavin (Rf), or vitamin B2, is an essential dietary component and represents the precursor of flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), which are important enzymatic cofactors required for terminal mitochondrial metabolism, and other cellular regulatory roles [1]. In different cells, Rf uptake occurs via specialized carrier-mediated processes performed by riboflavin transporter 1 (RFVT1; SLC52A1), RFVT2 (SLC52A2), and RFVT3 (SLC52A3) [2], belonging to the solute carrier family 52 (SLC52). Inside the cells, Rf is phosphorylated to FMN by riboflavin kinase (RFK, EC 2.7.1.26), and it is subsequently metabolized by FAD synthase (FADS, EC 2.7.7.2) to FAD, the flavin cofactor mainly located in mitochondria [1]. Rf pathway is gaining importance in the field of cancer therapy, since photoproducts are useful in preventing proliferation and metastasis of solid tumors [1]. An aberrant expression of RFVT3 is associated with stepwise development of esophageal squamous cell carcinoma (ESCC) [3]. Furthermore, a low intake of dietary Rf can lead to the development of colorectal cancer (CRC). Our group has demonstrated that alterations of transcription/translation of RFVTs make colon cancer cells greedy for the vitamin [4]. Here, we point our attention on the possible involvement of flavin cofactor homeostasis in other types of human cancer. To do this, we used both model cell lines and human biopsies. We correlated the altered expression of the three transporters with the increase of Rf-derived cofactor levels. The biochemical consequences of altering cellular flavoproteome will be discussed.