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Updated: Feb 21, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

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Secretory stressors induce intracellular death receptor accumulation to control apoptosis

Bram J van Raam1, Tamara Lacina1, Ralph K Lindemann2

  • 1Metabolism and Signaling in Cancer, BioMed X Innovation Center, Im Neuenheimer Feld 583, Heidelberg 69120, Germany.

Cell Death & Disease
|October 6, 2017
PubMed

Insights

Golgi stress induces death receptors (DRs) 4 and 5, initiating programmed cell death. This highlights the Golgi apparatus

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Programmed cell death, or apoptosis, is crucial for development and homeostasis.
  • The Golgi apparatus' role in cell death signaling is not fully understood.
  • Death receptors (DRs) mediate apoptosis upon ligand binding.

Purpose of the Study:

  • To characterize the programmed cell death induced by Golgi apparatus disruption.
  • To investigate the role of DR4 and DR5 in Golgi stress-induced apoptosis.
  • To explore the implications for cancer therapy.

Main Methods:

  • Pharmacological induction of Golgi stress.
  • Analysis of death receptor (DR4/DR5) expression and localization.
  • Assessment of cell susceptibility to TRAIL (tumor necrosis factor related apoptosis inducing ligand).
  • Investigation of CFLAR (caspase-8 and FADD-like apoptosis regulator) involvement.

Main Results:

  • Golgi stress induces DR4 and DR5 expression.
  • DR4 is primarily responsible for Golgi stress-induced cell death.
  • DR5 plays a more significant role in ER stress-induced cell death in certain cancer lines.
  • DR4 accumulates intracellularly, not on the cell surface.
  • Cells treated with secretory pathway stressors show increased TRAIL susceptibility due to CFLAR sequestration.

Conclusions:

  • The Golgi apparatus acts as a platform for cell death signaling.
  • Golgi stress triggers a unique apoptotic pathway involving DR4.
  • Findings suggest potential therapeutic strategies using DR agonists for cancer treatment.
  • Understanding Golgi-mediated apoptosis enhances knowledge of DR signaling.

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