The CD95/CD95L signaling pathway: a role in carcinogenesis.
Apoptosis is a fundamental process that contributes to tissue homeostasis, immune responses, and development. The receptor CD95, also called Fas, is a member of the tumor necrosis factor receptor (TNF-R) superfamily. Its cognate ligand, CD95L, is implicated in immune homeostasis and immune surveillance, and various lineages of malignant cells exhibit loss-of-function mutations in this pathway; therefore, CD95 was initially classified as a tumor suppressor gene. However, more recent data indicate that in different pathophysiological contexts, this receptor can transmit non-apoptotic signals, promote inflammation, and contribute to carcinogenesis. A comparison with the initial molecular events of the TNF-R signaling pathway leading to non-apoptotic, apoptotic, and necrotic pathways reveals that CD95 is probably using different molecular mechanisms to transmit its non-apoptotic signals (NF-κB, MAPK, and PI3K). As discussed in this review, the molecular process by which the receptor switches from an apoptotic function to an inflammatory role is unknown. More importantly, the biological functions of these signals remain elusive.
Université Rennes-1, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France; INSERM U1085, IRSET, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France; Equipe Labellisée Ligue Contre Le Cancer "Death Receptors and Tumor Escape", 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France; Centre Eugène Marquis, rue bataille Flandres Dunkerque, Rennes, France.
Amélie
A
Fouqué
Université Rennes-1, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France; INSERM U1085, IRSET, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France; Equipe Labellisée Ligue Contre Le Cancer "Death Receptors and Tumor Escape", 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France; Centre Eugène Marquis, rue bataille Flandres Dunkerque, Rennes, France.
Laure
L
Debure
Université Rennes-1, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France; INSERM U1085, IRSET, 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France; Equipe Labellisée Ligue Contre Le Cancer "Death Receptors and Tumor Escape", 2 Avenue du Professeur Léon Bernard, 35043 Rennes, France; Centre Eugène Marquis, rue bataille Flandres Dunkerque, Rennes, France. Electronic address: patrick.legembre@inserm.fr.
Patrick
P
Legembre
D000818:Animals; D063646:Carcinogenesis / Q000235:genetics*; D053222:Fas Ligand Protein / Q000502:physiology*; D006801:Humans; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D019014:fas Receptor / Q000502:physiology*
D053222:Fas Ligand Protein; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor
Apoptosis; Carcinogenesis; Cytokine; Fas; Inflammation