2024-03-29T12:16:53Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1547152021-12-28T16:20:56Zcom_10261_86com_10261_1col_10261_339
DIGITAL.CSIC
author
Bartolomé, Rubén Álvaro
author
Peláez-García, Alberto
author
Gómez, Inmaculada
author
Torres, Sofía
author
Fernandez-Aceñero, M. Jesús
author
Escudero-Paniagua, B.
author
Imbaud, Juan Ignacio
author
Casal, J. Ignacio
funder
Ministerio de Economía y Competitividad (España)
funder
Comunidad de Madrid
funder
Instituto de Salud Carlos III
2017-09-04T11:06:55Z
2017-09-04T11:06:55Z
2014-12-12
0021-9258
http://hdl.handle.net/10261/154715
10.1074/jbc.M114.600502
1083-351X
http://dx.doi.org/10.13039/501100003329http://dx.doi.org/10.13039/501100004587http://dx.doi.org/10.13039/100012818
25336636
Little 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.
eng
openAccess
Cadherin
Cell signalling
Colon cancer
Integrin
RGD Motif
Tumor Metastasis
An RGD motif present in cadherin 17 induces integrin activation and tumor growth
artículo
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URL
https://digital.csic.es/bitstream/10261/154715/1/J.%20Biol.%20Chem.-2014-Bartolom%c3%a9-34801-14.pdf
File
MD5
c427aaba0944ba35e2de8c06c333d18b
4957645
application/pdf
J. Biol. Chem.-2014-Bartolomé-34801-14.pdf