RT Journal Article
T1 Endothelial cell activation on 3D-matrices derived from PDGF-BB-stimulated fibroblasts is mediated by Snail1
A1 Herrera, Alberto
A1 Herrera, Mercedes
A1 Guerra Pérez, Natalia
A1 Galindo-Pumariño, Critina
A1 Larriba, Jesus
A1 García Barberán, Vanesa
A1 Gil, Beatriz
A1 Giménez-Moyano, Sara
A1 Ferreiro-Monteagudo, Reyes
A1 Veguillas, Pilar
A1 Candia, Antonio
A1 Peña, Raul
A1 Pinto, Jesus
A1 García-Bermejo, Laura
A1 Muñoz, Alberto
A1 García de Herreros, Antonio
A1 Bonilla, Felix
A1 Carrato, Antonio
A1 Peña, Cristina
AB Carcinomas, such as colon cancer, initiate their invasion by rescuing the innate plasticity of both epithelial cells and stromal cells. Although Snail is a transcriptional factor involved in the Epithelial-Mesenchymal Transition, in recent years, many studies have also identified the major role of Snail in the activation of Cancer-Associated Fibroblast (CAF) cells and the remodeling of the extracellular matrix. In CAFs, Platelet-derived growth factor (PDGF) receptor signaling is a major functional determinant. High expression of both SNAI1 and PDGF receptors is associated with poor prognosis in cancer patients, but the mechanism(s) that underlie these connections are not understood. In this study, we demonstrate that PDGF-activated fibroblasts stimulate extracellular matrix (ECM) fiber remodeling and deposition. Furthermore, we describe how SNAI1, through the FAK pathway, is a necessary factor for ECM fiber organization. The parallel-oriented fibers are used by endothelial cells as “tracks”, facilitating their activation and the creation of tubular structures mimicking in vivo capillary formation. Accordingly, Snail1 expression in fibroblasts was required for the coadjuvant effect of these cells on matrix remodeling and neoangiogenesis when co-xenografted in nude mice. Finally, in tumor samples from colorectal cancer patients a direct association between stromal SNAI1 expression and the endothelial marker CD34 was observed. In summary, our results advance the understanding of PDGF/SNAI1-activated CAFs in matrix remodeling and angiogenesis stimulation.
PB Springer Nature
SN 2157-9024
YR 2018
FD 2018
LK https://hdl.handle.net/20.500.14352/97598
UL https://hdl.handle.net/20.500.14352/97598
LA eng
NO Herrera, A., Herrera, M., Guerra-Perez, N. et al. Endothelial cell activation on 3D-matrices derived from PDGF-BB-stimulated fibroblasts is mediated by Snail1. Oncogenesis 7, 76 (2018). https://doi.org/10.1038/s41389-018-0085-z
DS Docta Complutense
RD 8 abr 2025