Over-expressing CYLD augments antitumor activity of TRAIL by inhibiting the NF-κB survival signaling in lung cancer cells

Neoplasma. 2012;59(1):18-29. doi: 10.4149/neo_2012_003.


The death ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) can selectively induce apoptosis in tumor cells. But studies have demonstrated that many tumor cells were resistant to TRAIL-induced apoptosis. CYLD is recognized as a negative regulator of nuclear factor-kappa B(NF-κB) activity. To explore a correlation between CYLD expression and responsiveness to TRAIL in lung cancer cell lines, we established lung cancer cell lines that stably express CYLD. Our data provided the first evidence that increased expression of CYLD directly blocks TRAIL-induced NF-κB activation, and consequently increases TRAIL-induced apoptosis in lung cancer cells. CYLD may act as a therapeutic target of lung cancer. Targeting CYLD, in combination with TRAIL, may be a new strategy to treat lung cancer with high NF-κB activity.

MeSH terms

  • Adenocarcinoma / pathology*
  • Antineoplastic Agents / pharmacology
  • Apoptosis / drug effects
  • Cell Line, Tumor / drug effects
  • Cell Line, Tumor / metabolism
  • Clinical Trials as Topic
  • Deubiquitinating Enzyme CYLD
  • Down-Regulation
  • Drug Resistance, Neoplasm
  • Gene Expression Regulation, Neoplastic
  • Genetic Vectors
  • Humans
  • Inhibitor of Apoptosis Proteins / biosynthesis
  • Inhibitor of Apoptosis Proteins / genetics
  • Lentivirus
  • Lung Neoplasms / pathology*
  • Molecular Targeted Therapy
  • NF-kappa B / metabolism*
  • Neoplasm Proteins / physiology*
  • Real-Time Polymerase Chain Reaction
  • Recombinant Fusion Proteins / pharmacology
  • Recombinant Fusion Proteins / physiology
  • Signal Transduction / drug effects
  • TNF-Related Apoptosis-Inducing Ligand / pharmacology*
  • Tumor Suppressor Proteins / physiology*


  • Antineoplastic Agents
  • Inhibitor of Apoptosis Proteins
  • NF-kappa B
  • Neoplasm Proteins
  • Recombinant Fusion Proteins
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Tumor Suppressor Proteins
  • CYLD protein, human
  • Deubiquitinating Enzyme CYLD