English   español  
Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/154715
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

An RGD motif present in cadherin 17 induces integrin activation and tumor growth

AuthorsBartolomé, Rubén Álvaro ; Peláez-García, Alberto ; Gomez, Inmaculada; Torres, Sofía ; Fernandez-Aceñero, M. Jesús; Escudero-Paniagua, B. ; Imbaud, Juan Ignacio; Casal, J. Ignacio
KeywordsCadherin
Cell Signaling
Colon Cancer
Integrin
RGD Motif
Tumor Metastasis
Issue Date12-Dec-2014
PublisherAmerican Society for Biochemistry and Molecular Biology
AbstractLittle is known about the mechanism of integrin activation by cadherin 17 (CDH17). Here we observed the presence of a tri-peptide motif, RGD, in domain 6 of the human CDH17 sequence and other cadherins such as cadherin 5 and cadherin 6. The use of CDH17 RAD mutants demonstrated a considerable decrease of proliferation and adhesion in RKO and KM12SM colon cancer cells. Furthermore, RGD peptides inhibited the adhesion of both cell lines to recombinant CDH17 domain 6. The RGD motif added exogenously to the cells provoked a change in β1 integrin to an active, high-affinity conformation and an increase in focal adhesion kinase and ERK1/2 activation. In vivo experiments with Swiss nude mice demonstrated that cancer cells expressing the CDH17 RAD mutant showed a considerable delay in tumor growth and liver homing. CDH17 RGD effects were also active in pancreatic cancer cells. Our results suggest that α2β1 integrin interacts with two different ligands, collagen IV and CDH17, using two different binding sites. In summary, the RGD binding motif constitutes a switch for integrin pathway activation and shows a novel capacity of CDH17 as an integrin ligand. This motif could be targeted to avoid metastatic dissemination in tumors overexpressing CDH17 and other RGD-containing cadherins.
Description15 p.-9 fig.
Publisher version (URL)http://dx.doi.org/10.1074/jbc.M114.600502
URIhttp://hdl.handle.net/10261/154715
DOI10.1074/jbc.M114.600502
ISSN0021-9258
E-ISSN1083-351X
Appears in Collections:(CIB) Artículos
Files in This Item:
File Description SizeFormat 
J. Biol. Chem.-2014-Bartolomé-34801-14.pdfArtículo principal4,84 MBAdobe 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.