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- Title
Loss of FADD protein expression results in a biased Fas-signaling pathway and correlates with the development of tumoral status in thyroid follicular cells.
- Authors
Tourneur, Lea; Mistou, Sylvie; Michiels, Francine-Marie; Devauchelle, Valerie; Renia, Laurent; Feunteun, Jean; Chiocchia, Gilles
- Abstract
Downregulation of proapoptotic molecules like Fas or caspase 8, or upregulation of antiapoptotic molecules like FLICE inhibitory protein has been suggested to be a regulatory mechanism set up by tumor cells to block the death signal received via death receptors. In an in-depth study of the Fas/FasL-signaling pathway in thyroid tumor development, we have demonstrated that tumor cells specifically downregulate the multideath receptor adapter Fas-associated death domain (FADD). The regulation of FADD expression occurred only at the protein level. Furthermore, in the absence of FADD, Fas-signaling resulted in accelerated growth of thyrocytes. Since thyrocytes also acquired FasL expression during tumor development, the absence of FADD protein could lead to greater resistance to numerous death receptor-mediated apoptosis, stimulation of their own proliferation through Fas/FasL interaction, and the capacity to counter-attack the infiltrating lymphocytes.Oncogene (2003) 22, 2795-2804. doi:10.1038/sj.onc.1206399
- Subjects
MOLECULES; PROTEINS; TUMORS
- Publication
Oncogene, 2003, Vol 22, Issue 18, p2795
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1206399