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Title

SPROUTY2 is a β-catenin and FOXO3a target gene indicative of poor prognosis in colon cancer

AuthorsOrdóñez-Morán, Paloma ; Barbáchano, Antonio ; Muñoz Terol, Alberto ; Pálmer, Héctor G.
KeywordsSPROUTY2
Wnt pathway
β-catenin
FOXO3a
Colon cancer
Issue Date10-Apr-2014
PublisherNature Publishing Group
CitationOncogene 33(15): 1975-1985 (2014)
AbstractSPROUTY2 (SPRY2) is an intracellular regulator of receptor tyrosine kinase signaling involved in cell growth, differentiation and tumorigenesis. Here, we show that SPRY2 is a target gene of the Wnt/β-catenin pathway that is abnormally activated in more than 90% of colon carcinomas. In human colon cancer cells, SPRY2 expression is induced by β-catenin in co-operation with the transcription factor FOXO3a instead of lymphoid enhancer factor/T-cell factor proteins. We found binding of β-catenin to the SPRY2 promoter at FOXO3a response elements. In vivo, cells marked by nuclear β-catenin and FOXO3a express SPRY2 in proliferative epithelial tissues, such as intestinal mucosa and epidermis. Consistently, inducible β-catenin deletion in mice reduced Spry2 expression in the small intestine. Moreover, SPRY2 protein expression correlated with nuclear β-catenin and FOXO3a colocalization in human colon carcinomas. Importantly, the amount of SPRY2 protein correlated with shorter overall survival of colon cancer patients. Our data reveal SPRY2 as a novel Wnt/β-catenin and FOXO3a target gene indicative of poor prognosis in colon cancer.
Descriptionet al.
Publisher version (URL)http://dx.doi.org/10.1038/onc.2013.140
URIhttp://hdl.handle.net/10261/96712
DOI10.1038/onc.2013.140
ISSN0950-9232
E-ISSN1476-5594
Appears in Collections:(IIBM) Artículos
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