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Role of monocarboxylate transporters in human cancers: state of the art
Open accessAbstract
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.
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“Lactate utilization by tumors is dependent on monocarboxylate transporters (MCTs) (Figure 3), which are highly expressed in a variety of tumors (Pinheiro et al., 2012).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Pinheiro et al., 2012
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Metadata
- Authors
- Pinheiro, C., Longatto-Filho, A., Azevedo-Silva, J., Casal, M., Schmitt, F. C., & Baltazar, F.
- Affiliations
- University of Minho (PT)
- Universidade do Porto (PT)
- Corresponding author
- Baltazar, Fátima
- Venue
- Journal of Bioenergetics and Biomembranes
- Published
- 2012-02
- Volume
- 44
- Issue
- 1
- Pages
- 127-139
- ISSN
- 0145-479X (ISSN-L)
- 1573-6881
- OpenAlex
- W2064926668
- Cited by
- 368
- References
- 118
- Citations by year
- 2026: 4 · 2025: 10 · 2024: 13 · 2023: 23 · 2022: 20 · 2021: 32 · 2020: 34 · 2019: 40 · 2018: 24 · 2017: 33 · 2016: 35 · 2015: 30 · 2014: 33 · 2013: 28 · 2012: 9
- FWCI
- 2.41
- Type
- journal article
- Language
- en
- Open access
- green
- hdl.handle.net
- Licence
- other-oa
- www.springer.com/tdm (tdm)
- Locations
- Journal of Bioenergetics and Biomembranes (publishedVersion)
- PubMed (publishedVersion)
- Portuguese National Funding Agency for Science, Research and Technology (RCAAP Project by FCT) (submittedVersion, other-oa)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Hypoxia, and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- monocarboxylate transporters, lactate transport, pyruvate transport, tumor acidification, tumor microenvironment pH, glycolysis, proton symport, cancer therapy targets, solid tumors, colon cancer, breast cancer, lung cancer, gynecologic cancer, prostate cancer, gastric cancer
- MeSH terms
- Monocarboxylate Transport Protein 1, Amino Acid Sequence, Animals, Multigene Family, Glycolysis, Humans, Hydrogen-Ion Concentration, Molecular Sequence Data, Neoplasms, Phylogeny, Species Specificity, Lactic Acid, Monocarboxylic Acid Transporters, Symporters, Metabolic Networks and Pathways
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