2026-07-24T06:21:32Zhttps://repisalud.isciii.es/rest/oai/requestoai:repisalud.isciii.es:20.500.12105/152332025-06-17T11:16:51Zcom_20.500.12105_15322com_20.500.12105_2051com_20.500.12105_2052col_20.500.12105_16958col_20.500.12105_19616
Repisalud
author
Puerto-Camacho, Pilar
author
Díaz-Martín, Juan
author
Olmedo-Pelayo, Joaquín
author
Bolado-Carrancio, Alfonso
author
Salguero-Aranda, Carmen
author
Jordán-Pérez, Carmen
author
Esteban-Medina, Marina
author
Álamo-Álvarez, Inmaculada
author
Delgado-Bellido, Daniel
author
Lobo-Selma, Laura
author
Dopazo, Joaquín
author
Sastre, Ana
author
Alonso, Javier
author
Grünewald, Thomas G P
author
Bernabeu, Carmelo
author
Byron, Adam
author
Brunton, Valerie G
author
Amaral, Ana Teresa
author
Álava, Enrique De
funder
Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
funder
Fundación María García Estrada (Fundación MGE)
funder
Candela Ribera. Asociación contra el sarcoma de Ewing
funder
Unión Europea. Fondo Social Europeo (ESF/FSE)
funder
Regional Government of Andalusia (España)
funder
Fundación Mari Paz Jiménez Casado
funder
CRIS contra el Cáncer
funder
Instituto de Salud Carlos III
funder
Asociación Pablo Ugarte contra el cáncer infantil
funder
Asociación Todos somos Iván
funder
Fundación la Sonrisa de Alex para la investigación y el tratamiento del sarcoma de Ewing
funder
Centro de Investigación Biomédica en Red - CIBERONC (Cáncer)
funder
Juan de la Cierva Incorporacion fellowship
funder
University of Seville (España)
funder
Barbara and Wilfried Mohr Foundation
2022-11-28T15:19:36Z
2022-11-28T15:19:36Z
2022-08-04
Int J Mol Sci. 2022 Aug 4;23(15):8657.
10.3390/ijms23158657
1422-0067
International Journal of Molecular Sciences
35955799
http://hdl.handle.net/20.500.12105/15233
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.
eng
Ewing sarcoma
Endoglin
Extracellular matrix
Mechano-transduction
Endoglin and MMP14 Contribute to Ewing Sarcoma Spreading by Modulation of Cell-Matrix Interactions
research article
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