title: 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.
authors.affiliation: Department of Pharmacology and Clinical Pharmacology and Auckland Cancer Society Research Centre, University of Auckland, Auckland, 1142, New Zealand.
authors.forename: Nancy N
authors.initials: NN
authors.lastname: Jong
authors.forename: Mark J
authors.initials: MJ
authors.lastname: McKeage
mesh_terms: D000818:Animals; D027321:Anion Transport Proteins / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000378:metabolism* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001692:Biological Transport; D027682:Cation Transport Proteins / Q000378:metabolism*; D051246:Glucose Transport Proteins, Facilitative / Q000378:metabolism; D006801:Humans; D008670:Metals / Q000378:metabolism*; D000226:Mitochondrial ADP, ATP Translocases / Q000378:metabolism; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D027321:Anion Transport Proteins; D000970:Antineoplastic Agents; D027682:Cation Transport Proteins; D051246:Glucose Transport Proteins, Facilitative; D008670:Metals; D009363:Neoplasm Proteins; D000226:Mitochondrial ADP, ATP Translocases
keywords: SLC transporters; angiogenesis; cancer; cancer chemotherapy; metal transport and uptake