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

Ord��ez-Mor�n, P; Irmisch, A; Barb�chano, A; Chicote, I; Tenbaum, S; Landolfi, S; Tabernero, J; Huelsken, J; Mu�oz, A; P�lmer, H G

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/?-catenin pathway that is abnormally activated in more than 90% of colon carcinomas. In human colon cancer cells, SPRY2 expression is induced by ?-catenin in co-operation with the transcription factor FOXO3a instead of lymphoid enhancer factor/T-cell factor proteins. We found binding of ?-catenin to the SPRY2 promoter at FOXO3a response elements. In vivo, cells marked by nuclear ?-catenin and FOXO3a express SPRY2 in proliferative epithelial tissues, such as intestinal mucosa and epidermis. Consistently, inducible ?-catenin deletion in mice reduced Spry2 expression in the small intestine. Moreover, SPRY2 protein expression correlated with nuclear ?-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/?-catenin and FOXO3a target gene indicative of poor prognosis in colon cancer.

• Journal Article Type: Article
• Acceptance Date: Mar 4, 2013
• Online Publication Date: Apr 29, 2013
• Publication Date: Apr 10, 2014
• Deposit Date: Jan 13, 2021
• Journal: Oncogene
• Print ISSN: 0950-9232
• Electronic ISSN: 1476-5594
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 33
• Issue: 15
• Pages: 1975-1985
• DOI: https://doi.org/10.1038/onc.2013.140
• Keywords: Genetics; Cancer Research; Molecular Biology
• Public URL: https://nottingham-repository.worktribe.com/output/5224809
• Publisher URL: https://www.nature.com/articles/onc2013140