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

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

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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. © 2014 Macmillan Publishers Limited.
Original languageEnglish
Pages (from-to)1975-1985
JournalOncogene
Volume33
Issue number15
DOIs
Publication statusPublished - 10 Apr 2014

Keywords

  • colon cancer
  • FOXO3a
  • SPROUTY2
  • wnt pathway
  • β-catenin

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    Ordóñez-Morán, P., Irmisch, A., Barbáchano, A., Chicote, I., Tenbaum, S., Landolfi, S., Tabernero, J., Huelsken, J., Muñoz, A., & Pálmer, H. G. (2014). SPROUTY2 is a β-catenin and FOXO3a target gene indicative of poor prognosis in colon cancer. Oncogene, 33(15), 1975-1985. https://doi.org/10.1038/onc.2013.140