Dependence receptor TrkC is a putative colon cancer tumor suppressor.
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| 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.
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| Authors | Anne-Laure Genevois, Gabriel Ichim, Marie-May Coissieux, Marie-Pierre Lambert, Fabrice Lavial, David Goldschneider, Loraine Jarrosson-Wuilleme, Florian Lepinasse, Géraldine Gouysse, Zdenko Herceg, Jean-Yves Scoazec, Servane Tauszig-Delamasure, Patrick Mehlen |
| Journal | Proceedings of the National Academy of Sciences of the United States of America (Proc Natl Acad Sci U S A) Vol. 110 Issue 8 Pg. 3017-22 (Feb 19 2013) ISSN: 1091-6490 [Electronic] United States |
| PMID | 23341610 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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