@article {763,
	title = {Endoglin and MMP14 Contribute to Ewing Sarcoma Spreading by Modulation of Cell-Matrix Interactions.},
	journal = {Int J Mol Sci},
	volume = {23},
	year = {2022},
	month = {2022 Aug 04},
	abstract = {<p>Endoglin (ENG) is a mesenchymal stem cell (MSC) marker typically expressed by active endothelium. This transmembrane glycoprotein is shed by matrix metalloproteinase 14 (MMP14). Our previous work demonstrated potent preclinical activity of first-in-class anti-ENG antibody-drug conjugates as a nascent strategy to eradicate Ewing sarcoma (ES), a devastating rare bone/soft tissue cancer with a putative MSC origin. We also defined a correlation between ENG and MMP14 expression in ES. Herein, we show that ENG expression is significantly associated with a dismal prognosis in a large cohort of ES patients. Moreover, both ENG/MMP14 are frequently expressed in primary ES tumors and metastasis. To deepen in their functional relevance in ES, we conducted transcriptomic and proteomic profiling of in vitro ES models that unveiled a key role of ENG and MMP14 in cell mechano-transduction. Migration and adhesion assays confirmed that loss of ENG disrupts actin filament assembly and filopodia formation, with a concomitant effect on cell spreading. Furthermore, we observed that ENG regulates cell-matrix interaction through activation of focal adhesion signaling and protein kinase C expression. In turn, loss of MMP14 contributed to a more adhesive phenotype of ES cells by modulating the transcriptional extracellular matrix dynamics. Overall, these results suggest that ENG and MMP14 exert a significant role in mediating correct spreading machinery of ES cells, impacting the aggressiveness of the disease.</p>},
	keywords = {Bone Neoplasms, Endoglin, Humans, Matrix Metalloproteinase 14, Proteomics, Receptors, Growth Factor, Sarcoma, Ewing, Signal Transduction},
	issn = {1422-0067},
	doi = {10.3390/ijms23158657},
	author = {Puerto-Camacho, Pilar and Diaz-Martin, Juan and Olmedo-Pelayo, Joaqu{\'\i}n and Bolado-Carrancio, Alfonso and Salguero-Aranda, Carmen and Jord{\'a}n-P{\'e}rez, Carmen and Esteban-Medina, Marina and Alamo-Alvarez, Inmaculada and Delgado-Bellido, Daniel and Lobo-Selma, Laura and Dopazo, Joaquin and Sastre, Ana and Alonso, Javier and Gr{\"u}newald, Thomas G P and Bernabeu, Carmelo and Byron, Adam and Brunton, Valerie G and Amaral, Ana Teresa and de Alava, Enrique}
}
@article {521,
	title = {The protease MT1-MMP drives a combinatorial proteolytic program in activated endothelial cells.},
	journal = {FASEB J},
	volume = {26},
	year = {2012},
	month = {2012 Nov},
	pages = {4481-94},
	abstract = {<p>The mechanism by which proteolytic events translate into biological responses is not well understood. To explore the link of pericellular proteolysis to events relevant to capillary sprouting within the inflammatory context, we aimed at the identification of the collection of substrates of the protease MT1-MMP in endothelial tip cells induced by inflammatory stimuli. We applied quantitative proteomics to endothelial cells (ECs) derived from wild-type and MT1-MMP-null mice to identify the substrate repertoire of this protease in TNF-α-activated ECs. Bioinformatics analysis revealed a combinatorial MT1-MMP proteolytic program, in which combined rather than single substrate processing would determine biological decisions by activated ECs, including chemotaxis, cell motility and adhesion, and vasculature development. MT1-MMP-deficient ECs inefficiently processed several of these substrates (TSP1, CYR61, NID1, and SEM3C), validating the model. This novel concept of MT1-MMP-driven combinatorial proteolysis in angiogenesis might be extendable to proteolytic actions in other cellular contexts.</p>},
	keywords = {Animals, Blotting, Western, Combinatorial Chemistry Techniques, Computational Biology, Endothelial Cells, Gene Expression Regulation, Enzymologic, Inflammation, Matrix Metalloproteinase 14, Mice, Protein Array Analysis, Reverse Transcriptase Polymerase Chain Reaction, RNA Interference, RNA, Small Interfering, Transcriptome, Tumor Necrosis Factor-alpha},
	issn = {1530-6860},
	doi = {10.1096/fj.12-205906},
	author = {Koziol, Agnieszka and Gonzalo, Pilar and Mota, Alba and Poll{\'a}n, Angela and Lorenzo, Cristina and Colom{\'e}, Nuria and Montaner, David and Dopazo, Joaquin and Arribas, Joaqu{\'\i}n and Canals, Francesc and Arroyo, Alicia G}
}
