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- Title
Regulation of MT1-MMP Activity through Its Association with ERMs.
- Authors
Suárez, Henar; López-Martín, Soraya; Toribio, Víctor; Zamai, Moreno; Hernández-Riquer, M. Victoria; Genís, Laura; Arroyo, Alicia G.; Yáñez-Mó, María
- Abstract
Membrane-bound proteases play a key role in biology by degrading matrix proteins or shedding adhesion receptors. MT1-MMP metalloproteinase is critical during cancer invasion, angiogenesis, and development. MT1-MMP activity is strictly regulated by internalization, recycling, autoprocessing but also through its incorporation into tetraspanin-enriched microdomains (TEMs), into invadopodia, or by its secretion on extracellular vesicles (EVs). We identified a juxtamembrane positively charged cluster responsible for the interaction of MT1-MMP with ERM (ezrin/radixin/moesin) cytoskeletal connectors in breast carcinoma cells. Linkage to ERMs regulates MT1-MMP subcellular distribution and internalization, but not its incorporation into extracellular vesicles. MT1-MMP association to ERMs and insertion into TEMs are independent phenomena, so that mutation of the ERM-binding motif in the cytoplasmic region of MT1-MMP does not preclude its association with the tetraspanin CD151, but impairs the accumulation and coalescence of CD151/MT1-MMP complexes at actin-rich structures. Conversely, gene deletion of CD151 does not impact on MT1-MMP colocalization with ERM molecules. At the plasma membrane MT1-MMP autoprocessing is severely dependent on ERM association and seems to be the dominant regulator of the enzyme collagenolytic activity. This newly characterized MT1-MMP/ERM association can thus be of relevance for tumor cell invasion.
- Subjects
EXTRACELLULAR vesicles; EXTRACELLULAR matrix proteins; DELETION mutation; CELL membranes; CANCER treatment; CYTOSKELETAL proteins
- Publication
Cells (2073-4409), 2020, Vol 9, Issue 2, p348
- ISSN
2073-4409
- Publication type
Article
- DOI
10.3390/cells9020348