Publication: Monocarboxylate transporters as targets
and mediators in cancer therapy response
Authors
Baltazar, Fátima ; Pinheiro, C. ; Morais-Santos, F. ; Azevedo-Silva, J. ; Queirós, O. ; Preto, A. ; Casal, M.
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Publisher
F. Hernández y Juan F. Madrid. Universidad de Murcia: Departamento de Biología Celular e Histología
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DOI
https://doi.org/10.14670/HH-29.1511
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info:eu-repo/semantics/article
Description
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.
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.
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Citation
Histology and Histopathology, Vol. 29, n.º 12 (2014)
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