Cellular and Molecular Biology



Monocarboxylate transporters as targets and mediators in cancer therapy response

F. Baltazar1,2, C. Pinheiro1-4, F. Morais-Santos1,2, J. Azevedo-Silva5, O. Queirós5,6, A. Preto5 and M. Casal5

1Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal, 2ICVS/3B’s - PT Government Associate Laboratory, Braga/Guimarães, Portugal, 3Barretos School of Health Sciences, Dr. Paulo Prata – FACISB, Barretos, Sao Paulo, Brazil, 4Molecular Oncology Research Center, Barretos Cancer Hospital, Barretos, Sao Paulo, Brazil, 5CBMA - Center of Molecular and Environmental Biology, Department of Biology, University of Minho, Campus de Gualtar, Braga, Portugal and 6CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Gandra PRD, Portugal

Offprint requests to: Dr. Fátima Baltazar, Life and Health Sciences Research Institute, School of Health Sciences, University of Minho, 4710-057 Braga, Portugal. e-mail: fbaltazar@ecsaude.uminho.pt

Summary. Monocarboxylate transporters (MCTs) belong to a family of transporters, encoded by the SLC16 gene family, which is presently composed by 14 members, but only MCT1 to 4 have been biochemically characterized. They have important functions in healthy tissues, being involved in the transmembrane transport of lactic acid and other monocarboxylic acids in human cells. One of the recently recognized hallmarks of cancer is altered metabolism, with high rates of glucose consumption and consequent lactate production. To maintain this metabolic phenotype, cancer cells upregulate a series of plasma membrane proteins, including MCTs. MCT1 and MCT4, in particular, play a dual role in the maintenance of the metabolic phenotype of tumour cells. On one hand, they facilitate the efflux of lactate and, on the other hand, they contribute to the preservation of the intracellular pH, by co-transporting a proton. Thus, MCTs are attractive targets in cancer therapy, especially in cancers with a hyper-glycolytic and acid-resistant phenotype. Also recent evidence demonstrates that MCTs are involved in cancer cell uptake of chemotherapeutic agents, including 3-bromopyruvate. In this way, MCTs can act as “Trojan horses”, as their elevated expression in cancer cells can mediate the entry of this chemotherapeutic agent into the cells and selectively kill cancer cells. As a result, MCTs will be mediators of chemotherapeutic response, and their expression can be used as a molecular marker to predict response to chemotherapy. Histol Histopathol 29, 1511-1524 (2014)

Key words: Monocarboxylate transporters, Cancer therapy, Glycolysis, Molecular targets

DOI: 10.14670/HH-29.1511