Lactate shuttle: from substance exchange to regulatory mechanism

Hum Cell. 2022 Jan;35(1):1-14. doi: 10.1007/s13577-021-00622-z. Epub 2021 Oct 4.

Abstract

Lactate, as the product of glycolytic metabolism and the substrate of energy metabolism, is an intermediate link between cancer cell and tumor microenvironment metabolism. The exchange of lactate between the two cells via mono-carboxylate transporters (MCTs) is known as the lactate shuttle in cancer. Lactate shuttle is the core of cancer cell metabolic reprogramming between two cells such as aerobic cancer cells and hypoxic cancer cells, tumor cells and stromal cells, cancer cells and vascular endothelial cells. Cancer cells absorb lactate by mono-carboxylate transporter 1 (MCT1) and convert lactate to pyruvate via intracellular lactate dehydrogenase B (LDH-B) to maintain their growth and metabolism. Since lactate shuttle may play a critical role in energy metabolism of cancer cells, components related to lactate shuttle may be a crucial target for tumor antimetabolic therapy. In this review, we describe the lactate shuttle in terms of both substance exchange and regulatory mechanisms in cancer. Meanwhile, we summarize the difference of key proteins of lactate shuttle in common types of cancer.

Keywords: Glycolysis; LDH; Lactate shuttle; MCT; Metabolic reprogramming.

Publication types

  • Review

MeSH terms

  • Endothelial Cells / metabolism
  • Energy Metabolism*
  • Glycolysis
  • Humans
  • Isoenzymes / metabolism
  • Isoenzymes / physiology
  • L-Lactate Dehydrogenase / metabolism
  • L-Lactate Dehydrogenase / physiology
  • Lactates / metabolism*
  • Molecular Targeted Therapy
  • Monocarboxylic Acid Transporters / metabolism*
  • Monocarboxylic Acid Transporters / physiology
  • Neoplasms / etiology
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Pyruvic Acid / metabolism
  • Stromal Cells / metabolism
  • Symporters / metabolism
  • Symporters / physiology
  • Tumor Microenvironment

Substances

  • Isoenzymes
  • Lactates
  • Monocarboxylic Acid Transporters
  • Symporters
  • monocarboxylate transport protein 1
  • Pyruvic Acid
  • L-Lactate Dehydrogenase
  • lactate dehydrogenase 1