Multiple biological activities of lactic acid in cancer: influences on tumor growth, angiogenesis and metastasis
| Autor: | Suveera Dhup, Pierre Sonveaux, Rajesh Kumar Dadhich, Paolo E. Porporato |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2012 |
| Předmět: |
Biology
Metastasis 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Neoplasms Drug Discovery medicine Humans Glycolysis Neoplasm Invasiveness Monocarboxylate transporters Lactic Acid Neoplasm Metastasis Hypoxia Tumor metabolism 030304 developmental biology Pharmacology 0303 health sciences Neovascularization Pathologic Lactic acidosis Hypoxia-inducible factor-1 Drug Discovery3003 Pharmaceutical Science Cancer medicine.disease Warburg effect 3. Good health Lactic acid Biochemistry chemistry Anaerobic glycolysis 030220 oncology & carcinogenesis Cancer cell Lactate Nuclear factor-kb |
| Zdroj: | Current Pharmaceutical Design Scopus-Elsevier |
| ISSN: | 1381-6128 |
| DOI: | 10.2174/138161212799504902 |
| Popis: | High rate of glycolysis is a metabolic hallmark of cancer. While anaerobic glycolysis promotes energy production under hypoxia, aerobic glycolysis, the Warburg effect, offers a proliferative advantage through redirecting carbohydrate fluxes from energy production to biosynthetic pathways. To fulfill tumor cell needs, the glycolytic switch is associated with elevated glucose uptake and lactic acid release. Altered glucose metabolism is the basis of positron emission tomography using the glucose analogue tracer [18F]- fluorodeoxyglucose, a widely used clinical application for tumor diagnosis and monitoring. On the other hand, high levels of lactate have been associated with poor clinical outcome in several types of human cancers. Although lactic acid was initially considered merely as an indicator of the glycolytic flux, many evidences originally from the study of normal tissue physiology and more recently transposed to the tumor situation indicate that lactic acid, i.e. the lactate anion and protons, directly contributes to tumor growth and progression. Here, we briefly review the current knowledge pertaining to lactic acidosis and metastasis, lactate shuttles, the influence of lactate on redox homeostasis, lactate signaling and lactate-induced angiogenesis in the cancer context. The monocarboxylate transporters MCT1 and MCT4 have now been confirmed as prominent facilitators of lactate exchanges between cancer cells with different metabolic behaviors and between cancer and stromal cells. We therefore address the function and regulation of MCTs, highlighting MCT1 as a novel anticancer target. MCT1 inhibition allows to simultaneously disrupt metabolic cooperativity and angiogenesis in cancer with a same agent, opening a new path for novel anticancer therapies. |
| Databáze: | OpenAIRE |
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