Article ; Online: MCT4 and CD147 colocalize with MMP14 in invadopodia and support matrix degradation and invasion by breast cancer cells.
2024 Volume 137, Issue 8
Abstract: 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 ... ...
| Abstract | 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. |
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| MeSH term(s) | Humans ; Basigin/metabolism ; Basigin/genetics ; Monocarboxylic Acid Transporters/metabolism ; Monocarboxylic Acid Transporters/genetics ; Breast Neoplasms/metabolism ; Breast Neoplasms/pathology ; Breast Neoplasms/genetics ; Matrix Metalloproteinase 14/metabolism ; Matrix Metalloproteinase 14/genetics ; Podosomes/metabolism ; Female ; Cell Line, Tumor ; Neoplasm Invasiveness ; Extracellular Matrix/metabolism ; Cell Movement ; Muscle Proteins/metabolism ; Muscle Proteins/genetics ; Lysosomal Membrane Proteins/metabolism ; Lysosomal Membrane Proteins/genetics ; Gelatin/metabolism ; Microtubule-Associated Proteins/metabolism ; Microtubule-Associated Proteins/genetics ; Cell Membrane/metabolism ; Lysosomal-Associated Membrane Protein 1 |
| Chemical Substances | Basigin (136894-56-9) ; Monocarboxylic Acid Transporters ; Matrix Metalloproteinase 14 (EC 3.4.24.80) ; SLC16A4 protein, human ; BSG protein, human ; MMP14 protein, human (EC 3.4.24.80) ; Muscle Proteins ; LAMP1 protein, human ; Lysosomal Membrane Proteins ; Gelatin (9000-70-8) ; Microtubule-Associated Proteins ; Lysosomal-Associated Membrane Protein 1 |
| Language | English |
| Publishing date | 2024-04-30 |
| Publishing country | England |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural |
| ZDB-ID | 2993-2 |
| ISSN | 1477-9137 ; 0021-9533 |
| ISSN (online) | 1477-9137 |
| ISSN | 0021-9533 |
| DOI | 10.1242/jcs.261608 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
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