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Title

SPROUTY-2 regulation and tumorigenic action in colon cancer

AuthorsBarbáchano, Antonio ; Ordóñez-Morán, Paloma ; Larriba, María Jesús ; Pereira, Fábio; Segura, Miguel F.; Ferrer-Mayorga, Gemma ; González-Sancho, José Manuel ; Rojas, José María; Hernando, Eva; Pálmer, Héctor G.; Muñoz Terol, Alberto
Issue Date2013
PublisherSociedad Española de Bioquímica y Biología Molecular
CitationXXXVI Congreso SEBBM (2013)
AbstractSPROUTY-2 (SPRY2) is a modulator of receptor tyrosine kinase signalling, and therefore of cell growth and differentiation, with cell type-dependent tumor promoting or suppressive effects. Previously we reported that SPRY2 expression in colon cancer cells is inhibited by the active vitamin D metabolite 1alpha, 25-dihydroxyvitamin D3 through E-cadherin-dependent and -independent mechanisms. In turn, SPRY2 represses both basal and 1alpha, 25-dihydroxyvitamin D3-induced E-cadherin expression. Recent data indicate that in human colon cancer cells SPRY2 expression is induced by beta-catenin in cooperation with the transcription factor FOXO3a instead of TCF/LEF1 proteins. In colon cancer patients, SPRY2 is upregulated in undifferentiated high grade tumors and at the invasive front of low grade carcinomas, and SPRY2 protein expression correlates with nuclear beta-catenin and FOXO3a colocalization. Importantly, the amount of SPRY2 protein correlates with shorter overall survival of colon cancer patients. We have found that SPRY2 dysregulates tight junction and epithelial polarity genes via microRNA-200-dependent upregulation of the transcriptional repressor ZEB1, which provides a mechanistic basis for the tumorigenic role of SPRY2 in colon cancer. In conclusion, our data reveal SPRY2 as a novel Wnt/beta-catenin and FOXO3a target gene indicative of poor prognosis in colon cancer.
DescriptionResumen del póster presentado al XXXVI Congreso de la Sociedad Española de Bioquímica y Biología Molecular, celebrado en Madrid del 3 al 6 de septiembre de 2013.-- et al.
URIhttp://hdl.handle.net/10261/125394
Appears in Collections:(IIBM) Comunicaciones congresos
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