English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/130529
Share/Impact:
Statistics
logo share SHARE logo core CORE   Add this article to your Mendeley library MendeleyBASE

Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL
Exportar a otros formatos:

Title

Twist1-induced activation of human fibroblasts promotes matrix stiffness by upregulating palladin and collagen α1(VI)

AuthorsGarcía-Palmero, Irene ; Torres, Sofía ; Bartolomé, Rubén Álvaro ; Peláez-García, Alberto ; Larriba, María Jesús ; López-Lucendo, María F. ; Peña, Cristina; Escudero-Paniagua, B. ; Muñoz Terol, Alberto ; Casal, J. Ignacio
Issue Date2016
PublisherNature Publishing Group
CitationOncogene 35(40): 5224-5236 (2016)
AbstractThe transcription factor Twist1 is involved in the epithelial–mesenchymal transition and contributes to cancer metastasis through mostly unknown mechanisms. In colorectal cancer, Twist1 expression is mainly restricted to the tumor stroma. We found that human fibroblast cell lines stably transfected with Twist1 acquired characteristics of activated cancer-associated fibroblasts (CAFs), such as hyperproliferation, an increased ability to migrate and an alignment of the actin cytoskeleton. Further, Twist1-activated fibroblasts promoted increased matrix stiffness. Using quantitative proteomics, we identified palladin and collagen α1(VI) as two major mediators of the Twist1 effects in fibroblast cell lines. Co-immunoprecipitation studies indicated that palladin and Twist1 interact within the nucleus, suggesting that palladin could act as a transcription regulator. Palladin was found to be more relevant for the cellular biomechanical properties, orientation and polarity, and collagen α1(VI) for the migration and invasion capacity, of Twist1-activated fibroblasts. Both palladin and collagen α1(VI) were observed to be overexpressed in colorectal CAFs and to be associated with poor colorectal cancer patient survival and relapse prediction. Our results demonstrate that Twist1-expressing fibroblasts mimic the properties of CAFs present at the tumor invasive front, which likely explains the prometastatic activities of Twist1. Twist1 appears to require both palladin and collagen α1(VI) as downstream effectors for its prometastatic effects, which could be future therapeutic targets in cancer metastasis.
Publisher version (URL)http://dx.doi.org/10.1038/onc.2016.57
URIhttp://hdl.handle.net/10261/130529
DOI10.1038/onc.2016.57
ISSN0950-9232
E-ISSN1476-5594
Appears in Collections:(CIB) Artículos
(IIBM) Artículos
Files in This Item:
File Description SizeFormat 
accesoRestringido.pdf15,38 kBAdobe PDFThumbnail
View/Open
Show full item record
Review this work
 

Related articles:


WARNING: Items in Digital.CSIC are protected by copyright, with all rights reserved, unless otherwise indicated.