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FADD in Cancer: Mechanisms of Altered Expression and Function, and Clinical Implications

1
Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle upon Tyne NE2 4HH, UK
2
Departamento de Biología, Universidad Autónoma de Madrid, 28049 Madrid, Spain
3
Centro de Biología Molecular Severo Ochoa (CBMSO), 28049 Madrid, Spain
4
Centro de Investigaciones Biomédicas en Red de Enfermedades Raras (CIBERER), 28029 Madrid, Spain
5
IIS-Fundación Jiménez Díaz, 28040 Madrid, Spain
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Cancers 2019, 11(10), 1462; https://doi.org/10.3390/cancers11101462
Received: 12 August 2019 / Revised: 25 September 2019 / Accepted: 27 September 2019 / Published: 29 September 2019
FADD was initially described as an adaptor molecule for death receptor-mediated apoptosis, but subsequently it has been implicated in nonapoptotic cellular processes such as proliferation and cell cycle control. During the last decade, FADD has been shown to play a pivotal role in most of the signalosome complexes, such as the necroptosome and the inflammasome. Interestingly, various mechanisms involved in regulating FADD functions have been identified, essentially posttranslational modifications and secretion. All these aspects have been thoroughly addressed in previous reviews. However, FADD implication in cancer is complex, due to pleiotropic effects. It has been reported either as anti- or protumorigenic, depending on the cell type. Regulation of FADD expression in cancer is a complex issue since both overexpression and downregulation have been reported, but the mechanisms underlying such alterations have not been fully unveiled. Posttranslational modifications also constitute a relevant mechanism controlling FADD levels and functions in tumor cells. In this review, we aim to provide detailed, updated information on alterations leading to changes in FADD expression and function in cancer. The participation of FADD in various biological processes is recapitulated, with a mention of interesting novel functions recently proposed for FADD, such as regulation of gene expression and control of metabolic pathways. Finally, we gather all the available evidence regarding the clinical implications of FADD alterations in cancer, especially as it has been proposed as a potential biomarker with prognostic value. View Full-Text
Keywords: FADD; chromosomal alterations; mutations; polymorphisms; transcription factors; epigenetic regulation; posttranslational modifications; gene expression; metabolism; clinical implications FADD; chromosomal alterations; mutations; polymorphisms; transcription factors; epigenetic regulation; posttranslational modifications; gene expression; metabolism; clinical implications
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Marín-Rubio, J.L.; Vela-Martín, L.; Fernández-Piqueras, J.; Villa-Morales, M. FADD in Cancer: Mechanisms of Altered Expression and Function, and Clinical Implications. Cancers 2019, 11, 1462.

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