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http://hdl.handle.net/2445/201041
Title: | The transcription factor GATA6 enables self-renewal of colon adenoma stem cells by repressing BMP gene expression |
Author: | Whissell, Gavin Montagni, Elisa Martinelli, Paola Hernando Momblona, Xavier Sevillano, Marta Jung, Peter Cortina, Carme Calon, Alexandre Abulí, Anna Castells Garangou, Antoni Castellví Bel, Sergi Nacht, Ana Silvina Sancho, Elena Attolini, Camille Stephan-Otto Vicent, Guillermo P. Real, Francisco X. Batlle, Eduard |
Keywords: | Càncer colorectal Genètica Colorectal cancer Genetics |
Issue Date: | 22-Jun-2014 |
Publisher: | Springer Nature |
Abstract: | Aberrant activation of WNT signalling and loss of BMP signals represent the two main alterations leading to the initiation of colorectal cancer (CRC). Here we screen for genes required for maintaining the tumour stem cell phenotype and identify the zinc-finger transcription factor GATA6 as a key regulator of the WNT and BMP pathways in CRC. GATA6 directly drives the expression of LGR5 in adenoma stem cells whereas it restricts BMP signalling to differentiated tumour cells. Genetic deletion of Gata6 from mouse colon adenomas increases the levels of BMP factors, which signal to block self-renewal of tumour stem cells. In human tumours, GATA6 competes with ?-catenin/TCF4 for binding to a distal regulatory region of the BMP4 locus that has been linked to increased susceptibility to development of CRC. Hence, GATA6 creates an environment permissive for CRC initiation by lowering the threshold of BMP signalling required for tumour stem cell expansion. |
Note: | Versió postprint del document publicat a: https://doi.org/10.1038/ncb2992 |
It is part of: | Nature Cell Biology, 2014, vol. 16, num. 7 |
URI: | http://hdl.handle.net/2445/201041 |
Related resource: | https://doi.org/10.1038/ncb2992 |
ISSN: | 1476-4679 |
Appears in Collections: | Articles publicats en revistes (Institut de Recerca Biomèdica (IRB Barcelona)) |
Files in This Item:
File | Description | Size | Format | |
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Whissell_Nat Cell Biol_2014.pdf | 206.77 MB | Adobe PDF | View/Open |
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