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

Semin Cancer Biol. 2020 Feb:60:121-131. doi: 10.1016/j.semcancer.2019.06.004. Epub 2019 Jun 6.

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.

Keywords: Apoptosis; Calcium; Cytoskeleton; Migration; TNF.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Apoptosis
  • Calcium / metabolism
  • Cytoskeleton / metabolism
  • Cytotoxicity, Immunologic
  • Fas Ligand Protein / genetics
  • Fas Ligand Protein / metabolism*
  • Homeostasis
  • Humans
  • Immunomodulation
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Neoplasms / etiology*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Neoplasms / therapy
  • Neoplastic Stem Cells / immunology
  • Neoplastic Stem Cells / metabolism
  • Neoplastic Stem Cells / pathology
  • Protein Binding
  • Signal Transduction
  • fas Receptor / genetics
  • fas Receptor / metabolism*

Substances

  • FAS protein, human
  • FASLG protein, human
  • Fas Ligand Protein
  • fas Receptor
  • Calcium