Abstract
Extracellular matrix metalloproteinase inducer, also knowns as cluster of differentiation 147 (CD147) or basigin, is a widely distributed cell surface glycoprotein that is involved in numerous physiological and pathological functions, especially in tumor invasion and metastasis. Monocarboxylate transporters (MCTs) catalyze the proton-linked transport of monocarboxylates such as L-lactate across the plasma membrane to preserve the intracellular pH and maintain cell homeostasis. As a chaperone to some MCT isoforms, CD147 overexpression significantly contributes to the metabolic transformation of tumor. This overexpression is characterized by accelerated aerobic glycolysis and lactate efflux, and it eventually provides the tumor cells with a metabolic advantage and an invasive phenotype in the acidic tumor microenvironment. This review highlights the roles of CD147 and MCTs in tumor cell metabolism and the associated molecular mechanisms. The regulation of CD147 and MCTs may prove to be with a therapeutic potential for tumors through the metabolic modification of the tumor microenvironment.
Highlights
A majority of human tumors exhibit significantly higher glucose flux compared with adjacent normal tissues, and the glucose metabolism is characterized by increased aerobic glycolysis in the tumorous tissues [1,2,3,4]
Hypoxia could increase MCT4 mRNA and protein expression, as MCT4 promoter activity is stimulated by hypoxia via the presence of four potential hypoxia response elements in the MCT4 promoter [79]. This is consistent with the proposed role of MCT4 in pumping out lactic acid derived from glycolysis across the plasma membrane from cells; elevated MCT4 expression is often observed in tumor cells that rely almost www.impactjournals.com/oncotarget entirely on glycolysis for their energy metabolism [80]
Blocking cluster of differentiation 147 (CD147) with a targeted monoclonal antibody or silencing CD147 by siRNA resulted in the inhibition of the proliferation, invasiveness, angiogenesis, and metastatic potential of colon cancer cells and malignant melanoma cells [17, 96, 97]. These results potentially suggest that the protumoral action of CD147 is at least in part due to the interaction with MCT1/MCT4 to promote tumor cell glycolysis via increased glucose uptake, lactate release, and the production of adenosine triphosphate (ATP)
Summary
A majority of human tumors exhibit significantly higher glucose flux compared with adjacent normal tissues, and the glucose metabolism is characterized by increased aerobic glycolysis in the tumorous tissues [1,2,3,4]. CD147 has been shown to associate with cell surface expression and the appropriate location of MCTs as a chaperone in the energy metabolism of tumors, contributing to the tumor invasion and tumor metastasis [18,19,20,21].
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