CD95 ligand induces motility and invasiveness of apoptosis-resistant tumor cells

Bryan C. Barnhart, Patrick Legembre, Eric Pietras, Concetta Bubici, Guido Franzoso, Marcus E. Peter*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

221 Scopus citations

Abstract

The apoptosis-inducing death receptor CD95 (APO-1/Fas) controls the homeostasis of many tissues. Despite its apoptotic potential, most human tumors are refractory to the cytotoxic effects of CD95 ligand. We now show that CD95 stimulation of multiple apoptosis-resistant tumor cells by CD95 ligand induces increased motility and invasiveness, a response much less efficiently triggered by TNFα or TRAIL. Three signaling pathways resulting in activation of NF-κB, Erk1/2 and caspase-8 were found to be important to this novel activity of CD95. Gene chip analyses of a CD95-stimulated tumor cell line identified a number of potential survival genes and genes that are known to regulate increased motility and invasiveness of tumor cells to be induced. Among these genes, urokinase plasminogen activator was found to be required for the CD95 ligand-induced motility and invasiveness. Our data suggest that CD95L, which is found elevated in many human cancer patients, has tumorigenic activities on human cancer cells. This could become highly relevant during chemotherapy, which can cause upregulation of CD95 ligand by both tumor and nontumor cells.

Original languageEnglish (US)
Pages (from-to)3175-3185
Number of pages11
JournalEMBO Journal
Volume23
Issue number15
DOIs
StatePublished - Aug 4 2004

Keywords

  • Apoptosis
  • CD95
  • Gene chip
  • Invasiveness
  • NF-κB

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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