Transferrin receptors are carrier proteins for transferrin, which is an important chelator with a primary function of serum iron transportation, thus maintaining systemic and cellular iron homeostasis. There are two transferrin receptors that have been identified, TFR2 and TFRC. The first transferrin receptor (TFRC) is involved in iron uptake and cell growth regulation. TFRC is ubiquitously expressed in most active proliferating cell types. This receptor is capable of internalizing four ferric ions during one cycle of transferrin-mediated endocytosis. The second transferrin receptor (TFR2), as a homolog of TFRC, shares 45-66% similarity in the extracellular domain with TFRC. TFR2 is mainly expressed in tissues that are responsible for iron metabolism regulation, such as the liver and intestine. Both these receptors are transmembrane glycoproteins. Studies have found that TFR2 has a significantly decreased affinity (25-fold decrease) for transferrin compared with TFRC. However, the interactions between the transferrin peptide and these receptors are not well characterized.
TFRs are reported to be overexpressed in a number of malignant tissues. Targeting the TFRs has been shown to be effective in delivering many different therapeutic agents and causing cytotoxic effects in cancer cells in vitro and in vivo. Here, we have briefly summarized some of our current knowledge of human TRFs regarding the structure, receptor expression, roles in health and diseases and contribution to cancer therapy.
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