2024-03-29T01:58:32Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/967122016-02-17T21:26:06Zcom_10261_22com_10261_1col_10261_275
SPROUTY2 is a β-catenin and FOXO3a target gene indicative of poor prognosis in colon cancer
Ordóñez-Morán, Paloma
Barbáchano, Antonio
Muñoz Terol, Alberto
Pálmer, Héctor G.
Instituto de Salud Carlos III
European Commission
Red Temática de Investigación Cooperativa en Cáncer (España)
Ministerio de Economía y Competitividad (España)
Comunidad de Madrid
EMBO
SPROUTY2
Wnt pathway
β-catenin
FOXO3a
Colon cancer
et al.
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.
Experiments were supported by grants from Fondo Europeo de Desarrollo Regional-Instituto de Salud Carlos III and Spanish Cooperative Research Network on Cancer (RTICC) (FIS-PI081356, RD12/0036/0001, RD12/0036/0021 and RD12/0036/0012), Plan Nacional de Biomedicina, Ministerio de Economía y Competitividad (SAF-18302) and Comunidad de Madrid (S2010/BMD-2344 Colomics2). HGP was supported by the Miguel Servet Program, Instituto de Salud Carlos III (ISCIII) and PO-M by an EMBO research fellowship.
Peer reviewed
2014-05-14T12:50:11Z
2014-05-14T12:50:11Z
2014-04-10
artículo
http://purl.org/coar/resource_type/c_6501
Oncogene 33(15): 1975-1985 (2014)
0950-9232
http://hdl.handle.net/10261/96712
10.1038/onc.2013.140
1476-5594
http://dx.doi.org/10.13039/501100004587
http://dx.doi.org/10.13039/501100000780
http://dx.doi.org/10.13039/501100003329
http://dx.doi.org/10.13039/501100003043
http://dx.doi.org/10.13039/100012818
en
#PLACEHOLDER_PARENT_METADATA_VALUE#
S2010/BMD-2344/Colomics2
Preprint
http://dx.doi.org/10.1038/onc.2013.140
Sí
open
Nature Publishing Group