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CD95/Fas and metastatic disease: What does not kill you makes you stronger.
Seminars in Cancer Biology ( IF 12.1 ) Pub Date : 2019-06-06 , DOI: 10.1016/j.semcancer.2019.06.004
Jean Philippe Guégan 1 , Christophe Ginestier 2 , Emmanuelle Charafe-Jauffret 2 , Thomas Ducret 3 , Jean-François Quignard 3 , Pierre Vacher 4 , Patrick Legembre 1
Affiliation  

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.



中文翻译:

CD95 / Fas和转移性疾病:不能杀死您的东西会使您变得更强壮。

CD95(也称为Fas)是死亡受体的原型。但是,有证据表明,该受体主要实现非凋亡信号通路,例如NF-κB,MAPK和PI3K,这些通路与细胞迁移,分化,存活和细胞因子分泌有关。存在至少两种不同形式的CD95L。金属蛋白酶切割多聚集的跨膜配体(m-CD95 L)以释放同源三聚体可溶性配体(s-CD95 L)。与m-CD95 L不同,s-CD95 L及其受体CD95之间的相互作用无法触发细胞凋亡,而是促进钙依赖性细胞迁移,这有助于炎症性Th17细胞在狼疮患者受损器官中的积累,并有利于癌细胞侵略性。针对CD95 / CD95 L的促炎作用的新型抑制剂可能为患有慢性炎性疾病或癌症的患者提供有吸引力的治疗选择。这篇综述讨论了CD95 / CD95 L对在细胞迁移和转移中的作用。

更新日期:2019-06-06
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