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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-04

AUTHORS

P Ordóñez-Morán, A Irmisch, A Barbáchano, I Chicote, S Tenbaum, S Landolfi, J Tabernero, J Huelsken, A Muñoz, H G Pálmer

ABSTRACT

SPROUTY2 (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. More... »

PAGES

1975

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/onc.2013.140

DOI

http://dx.doi.org/10.1038/onc.2013.140

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1046983595

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/23624922


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