The DOI matches its Crossref record; 119 of the 119 references it cites were found in a registry or an index.
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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Cites
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HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption
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“The frequency and severity of tumor hypoxia and its association with malignant progression make the hypoxiainduced metabolic adaptations promising targets for cancer therapy (Dang & Semenza 1999).”
BackgroundTargeting lactate-fueled respiration selectively kills hypoxic tumor cells in mice
Sonveaux, P., Végran, F., Schroeder, T., Wergin, M., Verrax, J., Rabbani, Z. N., Saedeleer, C. J. D., Kennedy, K. M., Diepart, C., Jordan, B. F., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci36843 · Cited by 1,635
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The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation
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Tumor glycolysis as a target for cancer therapy: progress and prospects
Ganapathy‐Kanniappan, S., & Geschwind, J.-F. H. (2013) · Molecular Cancer · doi:10.1186/1476-4598-12-152 · Cited by 1,428
HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations
Semenza, G. L. (2013) · Journal of Clinical Investigation · doi:10.1172/jci67230 · Cited by 1,335
Targeting Metabolism for Cancer Therapy
Luengo, A., Gui, D. Y., & Vander Heiden, M. G. (2017) · Cell Chemical Biology · doi:10.1016/j.chembiol.2017.08.028 · Cited by 971
Monocarboxylate transporters in cancer
Payen, V. L., Mina, E., Hée, V. F. V., Porporato, P. E., & Sonveaux, P. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.07.006 · Cited by 688
San-Millán, I., & Brooks, G. A. (2016) · Carcinogenesis · doi:10.1093/carcin/bgw127 · Cited by 640
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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