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Open AccessJournal ArticleDOI

Tumor metabolism of lactate: the influence and therapeutic potential for MCT and CD147 regulation

Kelly M. Kennedy, +1 more
- 01 Jan 2010 - 
- Vol. 6, Iss: 1, pp 127-148
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TLDR
The possibility of metabolic modification of the tumor microenvironment via regulation or manipulation of MCT1 and CD147 may prove to be promising avenues of therapeutic options.
Abstract
Tumor metabolism consists of complex interactions between oxygenation states, metabolites, ions, the vascular network and signaling cascades. Accumulation of lactate within tumors has been correlated with poor clinical outcomes. While its production has negative implications, potentially contributing to tumor progression, the implications of the ability of tumors to utilize lactate can offer new therapeutic targets for the future. Monocarboxylate transporters (MCTs) of the SLC16A gene family influence substrate availability, the metabolic path of lactate and pH balance within the tumor. CD147, a chaperone to some MCT subtypes, contributes to tumor progression and metastasis. The implications and consequences of lactate utilization by tumors are currently unknown; therefore future research is needed on the intricacies of tumor metabolism. The possibility of metabolic modification of the tumor microenvironment via regulation or manipulation of MCT1 and CD147 may prove to be promising avenues of therapeutic options.

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Citations
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SLC transporters as therapeutic targets: emerging opportunities

TL;DR: Current and investigational drugs that modulate SLC transporters, as well as promising drug targets, are highlighted.
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Reexamining cancer metabolism: lactate production for carcinogenesis could be the purpose and explanation of the Warburg Effect

TL;DR: It is posited that in carcinogenesis, aberrant cell signaling due to exaggerated and continually high lactate levels yields an inappropriate positive feedback loop that increases glucose uptake, glycolysis, lactate production and release, decreases mitochondrial function and clearance and upregulates glyCOlytic enzyme and monocarboxylate transporter expression thereby supporting angiogenesis, immune escape, cell migration, metastasis and self-sufficient metabolism.
References
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Journal ArticleDOI

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TL;DR: This work has been supported by the Department of the Army and the National Institutes of Health, and the author acknowledges the support and encouragement of the National Cancer Institute.
Journal ArticleDOI

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Origin of cancer cells

Otto Warburg
Journal ArticleDOI

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TL;DR: This work has shown that the PGC-1 coactivators play a critical role in the maintenance of glucose, lipid, and energy homeostasis and are likely involved in the pathogenic conditions such as obesity, diabetes, neurodegeneration, and cardiomyopathy.
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