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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Jarrosson-wuilleme, Loraine Mehlen, Patrick Coissieux, Marie-may Goldschneider, David Ichim, Gabriel Lepinasse, Florian Gouysse, Géraldine Scoazec, Jean-yves Lavial, Fabrice Genevois, Anne-laure Lambert, Marie-pierre Herceg, Zdenko Tauszig-delamasure, Servane |
| Description | Author Affiliation: Genevois AL ( Apoptosis, Cancer and Development Laboratory, Equipe labellisée 'La Ligue,' Institut National de la Santé et de la Recherche Médicale Unité 1052, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 5286, Université de Lyon, Centre Léon Bérard, 69008 Lyon, France.); |
| Abstract | The TrkC neurotrophin receptor belongs to the functional dependence receptor family, members of which share the ability to induce apoptosis in the absence of their ligands. Such a trait has been hypothesized to confer tumor-suppressor activity. Indeed, cells that express these receptors are thought to be dependent on ligand availability for their survival, a mechanism that inhibits uncontrolled tumor cell proliferation and migration. TrkC is a classic tyrosine kinase receptor and therefore generally considered to be a proto-oncogene. We show here that TrkC expression is down-regulated in a large fraction of human colorectal cancers, mainly through promoter methylation. Moreover, we show that TrkC silencing by promoter methylation is a selective advantage for colorectal cell lines to limit tumor cell death. Furthermore, reestablished TrkC expression in colorectal cancer cell lines is associated with tumor cell death and inhibition of in vitro characteristics of cell transformation, as well as in vivo tumor growth. Finally, we provide evidence that a mutation of TrkC detected in a sporadic cancer is a loss-of-proapoptotic function mutation. Together, these data support the conclusion that TrkC is a colorectal cancer tumor suppressor. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 8 |
| Volume Number | 110 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2013-02-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Colonic Neoplasms Genetics Receptor, TrkC Apoptosis Cell Line, Tumor DNA Methylation Down-Regulation Genes, Tumor Suppressor Ligands Promoter Regions, Genetic Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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