Emerging roles of metal solute carriers in cancer mechanisms and treatment.

Abstract

The literature concerning the roles of metal transporting solute carriers in the development and progression of human cancer, and in the delivery of metal-containing anticancer drugs, chemical carcinogens and imaging agents, is reviewed. A range of different solute carrier families, including members from the SLC2A, SLC11A, SLC22A, SLC25A, SLC30A, SLC31A, SLC39A, SLC40A, SLC47A and SLCO1B families, and various metal substrates, including arsenic, copper, gadolinium, iron, platinum and zinc, have been implicated in these cancer-related transport processes. For example, the transport of platinum-based anticancer drugs has been reported to be influenced by the expression and activities of OCT1-3 (SLC22A1-3), OCTN1/2 (SLC22A4/5), CTR1/2 (SLC31A1/2) and MATE1/2 (SLC47A1/2) solute carriers. As another example, solute carriers mediate control over the availability of endogenous metal ions, such as copper, iron and zinc, may have key roles in regulating tumour angiogenesis, cell proliferation, epithelial-to-mesenchymal transition and aberrant MAPK and STAT-3 signal transduction in cancer. In conclusion, emerging mechanisms involving metal transporting solute carriers are being defined and seem likely to make major contributions to cancer development and progression, and to the delivery of anticancer and tumour imaging agents.