Understanding the Contribution of Lactate Metabolism in Cancer Progress: A Perspective from Isomers

SIMPLE SUMMARY: Lactate (L-lactate and D-lactate) is the main production of the Warburg effect, which is vital for carcinoma cell metabolism. This review retrospects the lactate isomer metabolism in the cancer progress. The related enzyme and proteins have been listed as prognostic biomarkers for cancers, and the lactate down-streamed molecular cancerogenic signaling is also introduced. This review will provide a new strategy for anticancer therapy that targets lactate metabolism. ABSTRACT: Lactate mediates multiple cell-intrinsic effects in cancer metabolism in terms of development, maintenance, and metastasis and is often correlated with poor prognosis. Its functions are undertaken as an energy source for neighboring carcinoma cells and serve as a lactormone for oncogenic signaling pathways. Indeed, two isomers of lactate are produced in the Warburg effect: L-lactate and D-lactate. L-lactate is the main end-production of glycolytic fermentation which catalyzes glucose, and tiny D-lactate is fabricated through the glyoxalase system. Their production inevitably affects cancer development and therapy. Here, we systematically review the mechanisms of lactate isomers production, and highlight emerging evidence of the carcinogenic biological effects of lactate and its isomers in cancer. Accordingly, therapy that targets lactate and its metabolism is a promising approach for anticancer treatment.