2024-03-29T08:19:35Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/92442022-11-07T11:51:16Zcom_20.500.12105_2152com_20.500.12105_2051com_20.500.12105_2144com_20.500.12105_2145col_20.500.12105_2153col_20.500.12105_2146
00925njm 22002777a 4500
dc
Suárez, Henar
author
López-Martín, Soraya
author
Toribio, Victor
author
Zamai, Moreno
author
Hernandez-Riquer, Maria Victoria
author
Genis, Laura
author
Arroyo, Alicia G
author
Yanez-Mo, Maria
author
2020-02
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.
Cells. 2020; 9(2):348
2073-4409
http://hdl.handle.net/20.500.12105/9244
32028690
10.3390/cells9020348
2073-4409
Cells
ERM
MT1-MMP
Extracellular vesicles
Tetraspanin enriched-microdomains
Regulation of MT1-MMP Activity through Its Association with ERMs