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Loss of FADD protein expression results in a biased Fas-signaling pathway and correlates with the development of tumoral status in thyroid follicular cells

Oncogene volume 22, pages 2795–2804 (2003)Cite this article

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.

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Abbreviations

AAC:

adenoma/adenocarcinoma

Daxx:

Fas death domain-associated protein

FADD:

Fas-associated protein with death domain

HP:

hyperplastic

NP:

nonpathological

NTG:

nontransgenic

TFC:

thyroid follicular cells

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Acknowledgements

The assistance of Gisèle Baudry in the animal care is gratefully acknowledged. This work was supported by the ‘Institut National de la Santé et de la Recherche Médicale’ (INSERM). F-M Michiels and J Feunteun are supported by the ‘Association pour la Recherche sur le Cancer’ (ARC).

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Authors and Affiliations

  1. Département d'Immunologie, Institut Cochin, INSERM U567, CNRS UMR 8104, IFR 116, Université René Descartes, 27 rue du fbg St-Jacques, Paris, 75014, France

    Léa Tourneur, Sylvie Mistou, Valérie Devauchelle, Laurent Renia & Gilles Chiocchia

  2. Laboratoire d'Oncologie Moléculaire, CNRS Unité de Recherche Associée 1158, Institut Gustave Roussy, 39 rue Camille Desmoulins, Villejuif, 94805, France

    Francine-Marie Michiels & Jean Feunteun

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  1. Léa Tourneur
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  2. Sylvie Mistou
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  7. Gilles Chiocchia
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Correspondence to Gilles Chiocchia.

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Tourneur, L., Mistou, S., Michiels, FM. et al. Loss of FADD protein expression results in a biased Fas-signaling pathway and correlates with the development of tumoral status in thyroid follicular cells. Oncogene 22, 2795–2804 (2003). https://doi.org/10.1038/sj.onc.1206399

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