期刊
FRONTIERS IN ONCOLOGY
卷 10, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2020.00231
关键词
lactate; warburg effect; monocarboxylate transporters; GPR81; metabolic fuel; lactate shuttles; signaling molecule
类别
资金
- Northern Portugal Regional Operational Programme (NORTE 2020) under the Portugal Partnership Agreement, through the European Regional Development Fund (FEDER) [NORTE-01-0145-FEDER-000013]
- Northern Portugal Regional Operational Programme (NORTE 2020) under the Portugal Partnership Agreement, through Competitiveness Factors Operational Programme (COMPETE) [NORTE-01-0145-FEDER-000013]
- National funds, through the Foundation for Science and Technology (FCT) [POCI-01-0145-FEDER-007038]
- FCT [SFRH/BPD/116784/2016, SFRH/BPD/117858/2016]
- Fundação para a Ciência e a Tecnologia [SFRH/BPD/116784/2016] Funding Source: FCT
To sustain their high proliferation rates, most cancer cells rely on glycolytic metabolism, with production of lactic acid. For many years, lactate was seen as a metabolic waste of glycolytic metabolism; however, recent evidence has revealed new roles of lactate in the tumor microenvironment, either as metabolic fuel or as a signaling molecule. Lactate plays a key role in the different models of metabolic crosstalk proposed in malignant tumors: among cancer cells displaying complementary metabolic phenotypes and between cancer cells and other tumor microenvironment associated cells, including endothelial cells, fibroblasts, and diverse immune cells. This cell metabolic symbiosis/slavery supports several cancer aggressiveness features, including increased angiogenesis, immunological escape, invasion, metastasis, and resistance to therapy. Lactate transport is mediated by the monocarboxylate transporter (MCT) family, while another large family of G protein-coupled receptors (GPCRs), not yet fully characterized in the cancer context, is involved in lactate/acidosis signaling. In this mini-review, we will focus on the role of lactate in the tumor microenvironment, from metabolic affairs to signaling, including the function of lactate in the cancer-cancer and cancer-stromal shuttles, as well as a signaling oncometabolite. We will also review the prognostic value of lactate metabolism and therapeutic approaches designed to target lactate production and transport.
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