CD147/Basigin Is Involved in the Development of Malignant Tumors and T-Cell-Mediated Immunological Disorders via Regulation of Glycolysis

Int J Mol Sci. 2023 Dec 11;24(24):17344. doi: 10.3390/ijms242417344.

Abstract

CD147/Basigin, a transmembrane glycoprotein belonging to the immunoglobulin superfamily, is a multifunctional molecule with various binding partners. CD147 binds to monocarboxylate transporters (MCTs) and supports their expression on plasma membranes. MTC-1 and MCT-4 export the lactic acid that is converted from pyruvate in glycolysis to maintain the intracellular pH level and a stable metabolic state. Under physiological conditions, cellular energy production is induced by mitochondrial oxidative phosphorylation. Glycolysis usually occurs under anaerobic conditions, whereas cancer cells depend on glycolysis under aerobic conditions. T cells also require glycolysis for differentiation, proliferation, and activation. Human malignant melanoma cells expressed higher levels of MCT-1 and MCT-4, co-localized with CD147 on the plasma membrane, and showed an increased glycolysis rate compared to normal human melanocytes. CD147 silencing by siRNA abrogated MCT-1 and MCT-4 membrane expression and disrupted glycolysis, inhibiting cancer cell activity. Furthermore, CD147 is involved in psoriasis. MCT-1 was absent on CD4+ T cells in CD147-deficient mice. The naïve CD4+ T cells from CD147-deficient mice exhibited a low capacity to differentiate into Th17 cells. Imiquimod-induced skin inflammation was significantly milder in the CD147-deficient mice than in the wild-type mice. Overall, CD147/Basigin is involved in the development of malignant tumors and T-cell-mediated immunological disorders via glycolysis regulation.

Keywords: CD147; glycolysis; immune disorder; malignant tumor; psoriasis.

Publication types

  • Review

MeSH terms

  • Animals
  • Basigin* / genetics
  • Basigin* / metabolism
  • Glycolysis
  • Humans
  • Immune System Diseases / genetics
  • Immune System Diseases / metabolism
  • Mice
  • Monocarboxylic Acid Transporters / genetics
  • Monocarboxylic Acid Transporters / metabolism
  • Neoplasms* / genetics
  • Neoplasms* / metabolism
  • RNA, Small Interfering / metabolism
  • T-Lymphocytes

Substances

  • Basigin
  • Monocarboxylic Acid Transporters
  • RNA, Small Interfering

Grants and funding

This work was partly supported by JSPS KAKENHI, grant numbers JP18K08272 and JP21K08329.