Kanekura, T. 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, 24, 17344.
Kanekura, T. 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, 24, 17344.
Kanekura, T. 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, 24, 17344.
Kanekura, T. 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, 24, 17344.
Abstract
CD147/Basigin, a transmembrane glycoprotein belonging to the immunoglobulin super family, is a multifunctional molecule with various binding partners. CD147 binds to monocarboxylate transporters (MCTs) and supports their expression on plasma membranes. MCTs play an important role in glycolysis, the enzymatic conversion of glucose to pyruvate and adenosine triphosphate (ATP). Pyruvate is further converted to lactic acid which is exported from the cytoplasm by MTC-1 and MCT-4 to maintain intracellular pH 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. Silencing of CD147 by siRNA abrogated the membrane expression of MCT-1 and MCT-4 and disrupted glycolysis, inhibiting cancer cell activity.
The differentiation of CD4+ T cells into Th17 cells is a pivotal process in the development of various immune disorders, including psoriasis. Studies using CD147-deficient mice demonstrated the involvement of CD147 in psoriasis. MCT-1 was absent on CD4+ T cells in CD147-deficient mice. Naïve CD4+ T-cells from CD147-deficient mice show low potential for differentiation into Th17 cells. Imiquimod-induced skin inflammation was significantly milder in CD147-deficient mice than in wild-type mice. These findings indicate that CD147/Basigin is involved in the development of malignant tumors and T cell mediated immunological disorders via regulation of glycolysis.
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