2011
DOI: 10.1073/pnas.1106123108
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CD147 subunit of lactate/H+symporters MCT1 and hypoxia-inducible MCT4 is critical for energetics and growth of glycolytic tumors

Abstract: Malignant tumors exhibit increased dependence on glycolysis, resulting in abundant export of lactic acid, a hypothesized key step in tumorigenesis. Lactic acid is mainly transported by two H + /lactate symporters, MCT1/MCT4, that require the ancillary protein CD147/Basigin for their functionality. First, we showed that blocking MCT1/2 in Ras-transformed fibroblasts with AR-C155858 suppressed lactate export, glycolysis, and tumor growth, whereas ectopic expression of MCT4 in these cells … Show more

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Cited by 377 publications
(365 citation statements)
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“…Accordingly, forced overexpression of either of the partners (resulting in the stabilization of both of them as previously reported in other systems) [13][14][15] was sufficient to promote TC migration (Figure 6f and Supplementary Figure 6C). The contribution of MCT1 to migration was seen with glucose or serum as chemoattractants but not with lactate or glutamine used at their relevant concentrations in culture media (Supplementary Figure 6B), explaining why others in non-metabolically controlled systems failed to detect MCT1-dependent migration other than random.…”
Section: Discussionsupporting
confidence: 78%
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“…Accordingly, forced overexpression of either of the partners (resulting in the stabilization of both of them as previously reported in other systems) [13][14][15] was sufficient to promote TC migration (Figure 6f and Supplementary Figure 6C). The contribution of MCT1 to migration was seen with glucose or serum as chemoattractants but not with lactate or glutamine used at their relevant concentrations in culture media (Supplementary Figure 6B), explaining why others in non-metabolically controlled systems failed to detect MCT1-dependent migration other than random.…”
Section: Discussionsupporting
confidence: 78%
“…In this study, we report that mitochondria deprived from glycolytic fuels stabilize the expression of MCT1 and of its chaperone protein CD147/basigin in human TCs, thus providing a functional complex known to be involved in the transport of monocarboxylic acids (through MCT1) and in the activation of matrix metalloproteinases (through CD147). 11,14,15 Upon glucose starvation, the complex promoted TC migration towards serum and glucose. Our study identifies a functional link between impaired mitochondrial activity and TC migration wherein the mitochondrion acts as a glucose sensor and signals via ROS MCT1-dependent TC escape to a more favorable metabolic environment.…”
Section: Discussionmentioning
confidence: 99%
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“…SLC16A3 encodes the monocarboxylate transporter 4 (MCT4), a lactate-proton symporter that regulates intracellular pH in cancer cells [19,20]. We investigated the expression levels of MCT4, the related monocarboxylate transporter 1 (MCT1) and the ancillary glycoprotein basigin (BSG) across the cell line panel.…”
Section: Expression Mct1 and Mct4 In Breast Cancer Cellsmentioning
confidence: 99%