SPROUTY2 is a β-catenin and FOXO3a target gene indicative of poor prognosis in colon cancer
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2014 |
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| Erschienen: |
2014 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:33 |
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| Enthalten in: |
Oncogene - 33(2014), 15 vom: 10. Apr., Seite 1975-85 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ordóñez-Morán, P [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 30.05.2014 Date Revised 25.11.2016 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/onc.2013.140 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM22705055X |
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| 100 | 1 | |a Ordóñez-Morán, P |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a SPROUTY2 is a β-catenin and FOXO3a target gene indicative of poor prognosis in colon cancer |
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| 500 | |a Date Revised 25.11.2016 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a FOXO3 protein, human |2 NLM | |
| 650 | 7 | |a Forkhead Box Protein O3 |2 NLM | |
| 650 | 7 | |a Forkhead Transcription Factors |2 NLM | |
| 650 | 7 | |a Intracellular Signaling Peptides and Proteins |2 NLM | |
| 650 | 7 | |a Membrane Proteins |2 NLM | |
| 650 | 7 | |a SPRY2 protein, human |2 NLM | |
| 650 | 7 | |a beta Catenin |2 NLM | |
| 700 | 1 | |a Irmisch, A |e verfasserin |4 aut | |
| 700 | 1 | |a Barbáchano, A |e verfasserin |4 aut | |
| 700 | 1 | |a Chicote, I |e verfasserin |4 aut | |
| 700 | 1 | |a Tenbaum, S |e verfasserin |4 aut | |
| 700 | 1 | |a Landolfi, S |e verfasserin |4 aut | |
| 700 | 1 | |a Tabernero, J |e verfasserin |4 aut | |
| 700 | 1 | |a Huelsken, J |e verfasserin |4 aut | |
| 700 | 1 | |a Muñoz, A |e verfasserin |4 aut | |
| 700 | 1 | |a Pálmer, H G |e verfasserin |4 aut | |
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