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Histol Histopathol. 2014 Dec;29(12):1511-24. doi: 10.14670/HH-29.1511. Epub 2014 Jun 12.

Monocarboxylate transporters as targets and mediators in cancer therapy response.

Author information

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

Abstract

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. 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.

PMID:
24921258
DOI:
10.14670/HH-29.1511
[Indexed for MEDLINE]

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