Title |
Bcl-2 is a critical mediator of intestinal transformation
|
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Published in |
Nature Communications, March 2016
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DOI | 10.1038/ncomms10916 |
Pubmed ID | |
Authors |
Maartje van der Heijden, Cheryl D. Zimberlin, Anna M. Nicholson, Selcuk Colak, Richard Kemp, Sybren L. Meijer, Jan Paul Medema, Florian R. Greten, Marnix Jansen, Douglas J. Winton, Louis Vermeulen |
Abstract |
Intestinal tumour formation is generally thought to occur following mutational events in the stem cell pool. However, active NF-κB signalling additionally facilitates malignant transformation of differentiated cells. We hypothesized that genes shared between NF-κB and intestinal stem cell (ISCs) signatures might identify common pathways that are required for malignant growth. Here, we find that the NF-κB target Bcl-2, an anti-apoptotic gene, is specifically expressed in ISCs in both mice and humans. Bcl-2 is dispensable in homeostasis and, although involved in protecting ISCs from radiation-induced damage, it is non-essential in tissue regeneration. Bcl-2 is upregulated in adenomas, and its loss or inhibition impairs outgrowth of oncogenic clones, because Bcl-2 alleviates apoptotic priming in epithelial cells following Apc loss. Furthermore, Bcl-2 expression in differentiated epithelial cells renders these cells amenable to clonogenic outgrowth. Collectively, our results indicate that Bcl-2 is required for efficient intestinal transformation following Apc-loss and constitutes a potential chemoprevention target. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United Kingdom | 1 | 50% |
Unknown | 1 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 50% |
Science communicators (journalists, bloggers, editors) | 1 | 50% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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France | 1 | <1% |
Unknown | 148 | 99% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 30 | 20% |
Student > Master | 22 | 15% |
Researcher | 21 | 14% |
Student > Doctoral Student | 14 | 9% |
Student > Bachelor | 12 | 8% |
Other | 26 | 17% |
Unknown | 24 | 16% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 37 | 25% |
Biochemistry, Genetics and Molecular Biology | 30 | 20% |
Medicine and Dentistry | 19 | 13% |
Immunology and Microbiology | 8 | 5% |
Nursing and Health Professions | 4 | 3% |
Other | 22 | 15% |
Unknown | 29 | 19% |