MCT4 and CD147 colocalize with MMP14 in invadopodia and support matrix degradation and invasion by breast cancer cells.

Expression levels of the lactate-H+ cotransporter MCT4 (also known as SLC16A3) and its chaperone CD147 (also known as basigin) are upregulated in breast cancers, correlating with decreased patient survival. Here, we test the hypothesis that MCT4 and CD147 favor breast cancer invasion through interdependent effects on extracellular matrix (ECM) degradation. MCT4 and CD147 expression and membrane localization were found to be strongly reciprocally interdependent in MDA-MB-231 breast cancer cells. Overexpression of MCT4 and/or CD147 increased, and their knockdown decreased, migration, invasion and the degradation of fluorescently labeled gelatin. Overexpression of both proteins led to increases in gelatin degradation and appearance of the matrix metalloproteinase (MMP)-generated collagen-I cleavage product reC1M, and these increases were greater than those observed upon overexpression of each protein alone, suggesting a concerted role in ECM degradation. MCT4 and CD147 colocalized with invadopodia markers at the plasma membrane. They also colocalized with MMP14 and the lysosomal marker LAMP1, as well as partially with the autophagosome marker LC3, in F-actin-decorated intracellular vesicles. We conclude that MCT4 and CD147 reciprocally regulate each other and interdependently support migration and invasiveness of MDA-MB-231 breast cancer cells. Mechanistically, this involves MCT4-CD147-dependent stimulation of ECM degradation and specifically of MMP-mediated collagen-I degradation. We suggest that the MCT4-CD147 complex is co-delivered to invadopodia with MMP14.

Meng S ，Sørensen EE ，Ponniah M ，Thorlacius-Ussing J ，Crouigneau R ，Larsen T ，Borre MT ，Willumsen N ，Flinck M ，Pedersen SF ... -  《-》

Monocarboxylate transporter 4 regulates maturation and trafficking of CD147 to the plasma membrane in the metastatic breast cancer cell line MDA-MB-231.

Gallagher SM ，Castorino JJ ，Wang D ，Philp NJ ... -  《CANCER RESEARCH》

Regulation of invadopodia formation and activity by CD147.

Grass GD ，Bratoeva M ，Toole BP 《-》

CD147 subunit of lactate/H+ symporters MCT1 and hypoxia-inducible MCT4 is critical for energetics and growth of glycolytic tumors.

Le Floch R ，Chiche J ，Marchiq I ，Naiken T ，Ilc K ，Murray CM ，Critchlow SE ，Roux D ，Simon MP ，Pouysségur J ... -  《-》

CD147 regulates the expression of MCT1 and lactate export in multiple myeloma cells.

Walters DK ，Arendt BK ，Jelinek DF 《-》