CD95/Fas and metastatic disease: What does not kill you makes you stronger

Abstract : CD95 (also known as Fas) is the prototype of death receptors; however, evidence suggests that this receptor mainly implements non-apoptotic signaling pathways such as NF-κB, MAPK, and PI3K that are involved in cell migration, differentiation, survival, and cytokine secretion. At least two different forms of CD95 L exist. The multi-aggregated transmembrane ligand (m-CD95 L) is cleaved by metalloproteases to release a homotrimeric soluble ligand (s-CD95 L). Unlike m-CD95 L, the interaction between s-CD95 L and its receptor CD95 fails to trigger apoptosis, but instead promotes calcium-dependent cell migration, which contributes to the accumulation of inflammatory Th17 cells in damaged organs of lupus patients and favors cancer cell invasiveness. Novel inhibitors targeting the pro-inflammatory roles of CD95/CD95 L may provide attractive therapeutic options for patients with chronic inflammatory disorders or cancer. This review discusses the roles of the CD95/CD95 L pair in cell migration and metastasis.
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Submitted on : Thursday, September 12, 2019 - 4:44:37 PM
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Jean Philippe Guégan, Christophe Ginestier, Emmanuelle Charafe-Jauffret, Thomas Ducret, Jean-François Quignard, et al.. CD95/Fas and metastatic disease: What does not kill you makes you stronger. Seminars in Cancer Biology, Elsevier, In press, ⟨10.1016/j.semcancer.2019.06.004⟩. ⟨hal-02179928⟩



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