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TRAIL signalling: decisions between life and death

Christina Falschlehner1, Christoph H Emmerich, Björn Gerlach

  • 1Division of Apoptosis Regulation (D040), Tumor Immunology Program, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 580, 69120 Heidelberg, Germany.

The International Journal of Biochemistry & Cell Biology
|April 4, 2007
PubMed

Insights

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively kills cancer cells, making it a promising biotherapeutic. This review details TRAIL

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in tumor cells.
  • TRAIL and agonistic antibodies targeting TRAIL-R1/TRAIL-R2 are promising cancer therapeutics.
  • TRAIL receptors include apoptosis-inducing (TRAIL-R1, TRAIL-R2) and non-apoptosis-inducing (TRAIL-R3, TRAIL-R4) types.

Purpose of the Study:

  • To review the signaling pathways initiated by TRAIL receptors.
  • To elucidate the interplay between apoptosis and non-apoptosis signaling in TRAIL pathways.
  • To summarize key findings on the TRAIL signaling network and its role in tumor cell fate.

Main Methods:

  • Review of existing literature on TRAIL signaling pathways.
  • Analysis of the formation and function of the TRAIL death-inducing signaling complex (DISC).
  • Examination of the interaction between extrinsic (TRAIL-mediated) and intrinsic apoptosis pathways.

Main Results:

  • DISC formation triggers a protease cascade leading to apoptosis.
  • TRAIL signaling involves crosstalk between extrinsic and intrinsic apoptosis pathways.
  • NF-kappaB, PKB/Akt, and MAPK pathways modulate both apoptotic and non-apoptotic TRAIL signaling.

Conclusions:

  • TRAIL-mediated apoptosis is a complex process involving multiple signaling pathways.
  • Understanding TRAIL signaling networks is crucial for developing effective cancer therapies.
  • The balance between apoptotic and non-apoptotic signaling determines tumor cell survival or death.

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