| DCC constrains tumour progression via its dependence receptor activity. | |
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MedLine Citation:
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PMID: 22158121 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The role of deleted in colorectal carcinoma (DCC) as a tumour suppressor has been a matter of debate for the past 15 years. DCC gene expression is lost or markedly reduced in the majority of advanced colorectal cancers and, by functioning as a dependence receptor, DCC has been shown to induce apoptosis unless engaged by its ligand, netrin-1 (ref. 2). However, so far no animal model has supported the view that the DCC loss-of-function is causally implicated as predisposing to aggressive cancer development. To investigate the role of DCC-induced apoptosis in the control of tumour progression, here we created a mouse model in which the pro-apoptotic activity of DCC is genetically silenced. Although the loss of DCC-induced apoptosis in this mouse model is not associated with a major disorganization of the intestines, it leads to spontaneous intestinal neoplasia at a relatively low frequency. Loss of DCC-induced apoptosis is also associated with an increase in the number and aggressiveness of intestinal tumours in a predisposing APC mutant context, resulting in the development of highly invasive adenocarcinomas. These results demonstrate that DCC functions as a tumour suppressor via its ability to trigger tumour cell apoptosis. |
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Authors:
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Marie Castets; Laura Broutier; Yann Molin; Marie Brevet; Guillaume Chazot; Nicolas Gadot; Armelle Paquet; Laetitia Mazelin; Loraine Jarrosson-Wuilleme; Jean-Yves Scoazec; Agnès Bernet; Patrick Mehlen |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-11 |
Journal Detail:
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Title: Nature Volume: - ISSN: 1476-4687 ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0410462 Medline TA: Nature Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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1] Apoptosis, Cancer and Development Laboratory - Equipe labellisée 'La Ligue', LabEx DEVweCAN, Centre de Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008 Lyon, France [2]. |
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