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Title

SPROUTY-2 and E-cadherin regulate reciprocally and dictate colon cancer cell tumourigenicity

AuthorsBarbáchano, Antonio ; Ordóñez-Morán, Paloma ; Pereira, Fábio; Larriba, María Jesús ; Bonilla, Félix; Pálmer, Héctor G.; Muñoz Terol, Alberto
Issue Date2010
PublisherNature Publishing Group
CitationOncogene 29(33): 4800-4813 (2010)
AbstractSPROUTY-2 (SPRY2) regulates receptor tyrosine kinase signalling and therefore cell growth and differentiation. In this study, we show that SPRY2 expression in colon cancer cells is inhibited by the active vitamin D metabolite 1α,25-dihydroxyvitamin D 3 (1,25(OH) 2 D 3) through E-cadherin-dependent and-independent mechanisms. In turn, SPRY2 represses both basal and 1,25(OH) 2 D 3-induced E-cadherin expression. In line with this, SPRY2 induces ZEB1 RNA and protein, but not that of other epithelial-to-mesenchymal transition inducers that repress the CDH1/E-cadherin promoter. Consistently, SPRY2 and E-cadherin protein levels inversely correlate in colon cancer cell lines and xenografted tumours. Moreover, SPRY2 knockdown by small hairpin RNA increases CDH1/E-cadherin expression and, reciprocally, CDH1/E-cadherin knockdown increases that of SPRY2. In colon cancer patients, SPRY2 is upregulated in undifferentiated high-grade tumours and at the invasive front of low-grade carcinomas. Quantification of protein expression in 34 tumours confirmed an inverse correlation between SPRY2 and E-cadherin. Our data demonstrate a tumourigenic action of SPRY2 that is based on the repression of E-cadherin, probably by the induction of ZEB1, and a reciprocal regulation of SPRY2 and E-cadherin that dictates cell phenotype. We propose SPRY2 as a candidate novel marker for high-grade tumours and a target of therapeutic intervention in colon cancer. © 2010 Macmillan Publishers Limited All rights reserved.
DescriptionEl pdf del artículo es la versión post-print.-- et al.
Publisher version (URL)http://dx.doi.org/10.1038/onc.2010.225
URIhttp://hdl.handle.net/10261/77896
DOI10.1038/onc.2010.225
Identifiersdoi: 10.1038/onc.2010.225
issn: 0950-9232
e-issn: 1476-5594
Appears in Collections:(IIBM) Artículos
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