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Updated: Jul 4, 2026

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex
07:17

Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex

Published on: August 2, 2021

Acquired resistance to Fas/CD95 ligation in U937 cells is associated with multiple molecular mechanisms

Jeanette Blomberg1, Kristina Ruuth, Daniel Santos

  • 1Department of Molecular Biology, Umeå University, S-90187 Umeå, Sweden.

Anticancer Research
|May 30, 2008
PubMed
Abstract

Insights

Acquired resistance to apoptosis in U937 cells involves impaired caspase-8 activation and reduced Fas expression. These changes confer cross-resistance to other death ligands, impacting cancer therapy.

Area of Science:

  • Cellular Biology
  • Molecular Oncology
  • Immunology

Background:

  • Acquired resistance to apoptosis is crucial in tumor development and therapy resistance.
  • Investigating resistance to Fas/CD95/Apo-1-induced apoptosis is vital for understanding treatment failure.

Purpose of the Study:

  • To generate a Fas ligand-resistant U937 cell line variant.
  • To elucidate the molecular mechanisms underlying acquired resistance to Fas-induced apoptosis.

Main Methods:

  • Generation of a Fas ligand-resistant U937 cell line.
  • Analysis of caspase-8 activation, Fas expression, and FADD expression.
  • Assessment of ligand-induced Fas aggregation.
  • Pharmacological inhibition of signaling pathways.
  • Evaluation of FLIP protein expression.

Main Results:

  • Fas resistance led to partial cross-resistance to TRAIL and TNF-alpha.
  • Impaired caspase-8 activation and reduced Fas expression were observed.
  • FADD expression and Fas aggregation remained intact.
  • Resistance correlated with altered tyrosine phosphatase/kinase activities and de novo protein synthesis.
  • Elevated expression of the anti-apoptotic protein FLIP was noted in resistant cells.

Conclusions:

  • Acquired resistance to Fas-induced apoptosis in U937 cells involves specific molecular mechanisms.
  • These mechanisms confer cross-resistance to other death ligands, impacting therapeutic strategies.

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