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Journal of Bioenergetics and Biomembranes

, Volume 44, Issue 1, pp 127–139 | Cite as

Role of monocarboxylate transporters in human cancers: state of the art

  • Céline Pinheiro
  • Adhemar Longatto-Filho
  • João Azevedo-Silva
  • Margarida Casal
  • Fernando C. Schmitt
  • Fátima BaltazarEmail author
MINI-REVIEW

Abstract

Monocarboxylate transporters (MCTs) belong to the SLC16 gene family, presently composed by 14 members. MCT1-MCT4 are proton symporters, which mediate the transmembrane transport of pyruvate, lactate and ketone bodies. The role of MCTs in cell homeostasis has been characterized in detail in normal tissues, however, their role in cancer is still far from understood. Most solid tumors are known to rely on glycolysis for energy production and this activity leads to production of important amounts of lactate, which are exported into the extracellular milieu, contributing to the acidic microenvironment. In this context, MCTs will play a dual role in the maintenance of the hyper-glycolytic acid-resistant phenotype of cancer, allowing the maintenance of the high glycolytic rates by performing lactate efflux, and pH regulation by the co-transport of protons. Thus, they constitute attractive targets for cancer therapy, which have been little explored. Here we review the literature on the role of MCTs in solid tumors in different locations, such as colon, central nervous system, breast, lung, gynecologic tract, prostate, stomach, however, there are many conflicting results and in most cases there are no functional studies showing the dependence of the tumors on MCT expression and activity. Additional studies on MCT expression in other tumor types, confirmation of the results already published as well as additional functional studies are needed to deeply understand the role of MCTs in cancer maintenance and aggressiveness.

Keywords

Monocarboxylate transporters Cancer Warburg effect Lactate 

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© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Céline Pinheiro
    • 1
    • 2
  • Adhemar Longatto-Filho
    • 1
    • 2
    • 3
  • João Azevedo-Silva
    • 4
  • Margarida Casal
    • 4
  • Fernando C. Schmitt
    • 5
    • 6
  • Fátima Baltazar
    • 1
    • 2
    Email author
  1. 1.Life and Health Sciences Research Institute (ICVS), School of Health SciencesUniversity of MinhoBragaPortugal
  2. 2.ICVS/3B’s - PT Government Associate LaboratoryBraga/GuimarãesPortugal
  3. 3.Laboratory of Medical Investigation (LIM) 14, Department of PathologyUniversity of São Paulo School of MedicineSão PauloBrazil
  4. 4.CBMA - Center of Molecular and Environmental Biology, Department of BiologyUniversity of MinhoBragaPortugal
  5. 5.Medical FacultyUniversity of PortoPortoPortugal
  6. 6.IPATIMUPInstitute of Molecular Pathology and Immunology of University of PortoPortoPortugal

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