title: Dependence receptor TrkC is a putative colon cancer tumor suppressor.
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.
authors: 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.
authors: Anne-Laure
authors: AL
authors: Genevois
authors: Gabriel
authors: G
authors: Ichim
authors: Marie-May
authors: MM
authors: Coissieux
authors: Marie-Pierre
authors: MP
authors: Lambert
authors: Fabrice
authors: F
authors: Lavial
authors: David
authors: D
authors: Goldschneider
authors: Loraine
authors: L
authors: Jarrosson-Wuilleme
authors: Florian
authors: F
authors: Lepinasse
authors: Géraldine
authors: G
authors: Gouysse
authors: Zdenko
authors: Z
authors: Herceg
authors: Jean-Yves
authors: JY
authors: Scoazec
authors: Servane
authors: S
authors: Tauszig-Delamasure
authors: Patrick
authors: P
authors: Mehlen
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics*; D019175:DNA Methylation; D015536:Down-Regulation; D016147:Genes, Tumor Suppressor; D006801:Humans; D008024:Ligands; D011401:Promoter Regions, Genetic; D000090063:Proto-Oncogene Mas; D020812:Receptor, trkC / Q000235:genetics*
chemical_list: D008024:Ligands; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D020812:Receptor, trkC