CD95/Fas, Non-Apoptotic Signaling Pathways, and Kinases

• Published in: Frontiers in immunology Vol. 8; p. 1216
• Main Authors: Le Gallo, Matthieu, Poissonnier, Amanda, Blanco, Patrick, Legembre, Patrick
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers 27.09.2017; Frontiers Media S.A
• Subjects: apoptosis; Cancer; Chemical Sciences; endothelium; Fas; FasL; Immunology; Life Sciences; lupus metastasis; migration; endothelium; FasL; tyrosine kinase; migration; Fas; apoptosis; lupus metastasis
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2017.01216

Endothelial cells lining new blood vessels that develop during inflammatory disorders or cancers act as doors that either allow or block access to the tumor or inflamed organ. Recent data show that these endothelial cells in cancer tissues and inflamed tissues of lupus patients overexpress CD95L, the biological role of which is a subject of debate. The receptor CD95 (also named Fas or apoptosis antigen 1) belongs to the tumor necrosis factor (TNF) receptor superfamily. Its cognate ligand, CD95L, is implicated in immune homeostasis and immune surveillance. Because mutations of this receptor or its ligand lead to autoimmune disorders such as systemic lupus erythematosus (SLE) and cancers, CD95 and CD95L were initially thought to play a role in immune homeostasis and tumor elimination apoptotic signaling pathways. However, recent data reveal that CD95 also evokes non-apoptotic signals, promotes inflammation, and contributes to carcinogenesis; therefore, it is difficult to dissect its apoptotic effects from its non-apoptotic effects during pathogenesis of disease. CD95L is cleaved by metalloproteases and so exists in two different forms: a transmembrane form and a soluble ligand (s-CD95L). We recently observed that the soluble ligand is overexpressed in serum from patients with triple-negative breast cancer or SLE, in whom it contributes to disease severity by activating non-apoptotic signaling pathways and promoting either metastatic dissemination or accumulation of certain T cell subsets in damaged organs. Here, we discuss the roles of CD95 in modulating immune functions induction of mainly non-apoptotic signaling pathways.