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| Status |
Public on Mar 30, 2015 |
| Title |
DICKKOPF-1 locates in the nucleus of human differentiated epithelial intestinal and mammary cells and regulates gene expression |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Wnt/b-catenin pathway is a key modulator of intestinal homeostasis by regulating stem cell biology during gut organogenesis and in adult life. DICKKOPF (DKK)-1 is a secreted inhibitor of Wnt/b-catenin signaling from plasma membrane receptors. We found that in human intestine, DKK-1 locates within the nucleus of differentiated enterocytes and enteroendocrine cells but not of proliferating and stem cells at the bottom of the crypts. DKK-1 is also nuclear in colon cancer cells locating at sites of active gene transcription. ChIP-seq and transcriptomic analysis both confirmed that DKK-1 binds chromatin and regulates gene expression. Thus, we demonstrate that DKK-1 is a multifunctional protein that inhibits Wnt/b-catenin signaling at plasma membrane and controls specific genes in the nucleus, suggesting that these functions are relevant for intestinal homeostasis.
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| Overall design |
Analysis of DKK-1 location and associated roles in human colon cancer cells and crypts of small and large bowel.
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| Contributor(s) |
Aguilera O, González-Sancho JM, Fernandez AF, Zazo S, Tapia O, Canals F, Aguilar S, Morte B, Huidobro C, Orgaz JL, Freije MP, Jiméne B, Graña O, Pisano D, Lafarga M, Fraga MF, Rojo F, López-Otin C, Muñoz A |
| Citation(s) |
25788273 |
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| Submission date |
Jan 23, 2012 |
| Last update date |
Apr 02, 2019 |
| Contact name |
beatriz Morte |
| E-mail(s) |
bmorte@iib.uam.es
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| Organization name |
CIBERER
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| Street address |
C/arturo Duperier 4
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| City |
Madrid |
| ZIP/Postal code |
28029 |
| Country |
Spain |
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| Platforms (1) |
| GPL6244 |
[HuGene-1_0-st] Affymetrix Human Gene 1.0 ST Array [transcript (gene) version] |
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| Samples (6)
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| GSM864825 |
DLD-1/Mock cells treated with DOX, control 1 |
| GSM864826 |
DLD-1/Mock cells treated with DOX, control-2 |
| GSM864827 |
DLD-1/Mock cells treated with DOX, control-3 |
| GSM864828 |
DLD-1/DKK1 cells treated with DOX, DKK1-1 |
| GSM864829 |
DLD-1/DKK1 cells treated with DOX, DKK1-2 |
| GSM864830 |
DLD-1/DKK1 cells treated with DOX, DKK1-3 |
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| Relations |
| BioProject |
PRJNA151563 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE35272_RAW.tar |
27.8 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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