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Updated: May 14, 2026

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

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

Published on: December 27, 2016

p58(IPK)-mediated attenuation of the proapoptotic PERK-CHOP pathway allows malignant progression upon low glucose

Anne-Laure Huber1, Justine Lebeau, Patricia Guillaumot

  • 1University of Lyon, 69000 Lyon, France.

Molecular Cell
|February 12, 2013
PubMed

Insights

Malignant cells facing glucose shortage activate the endoplasmic reticulum (ER) unfolded protein response (UPR), leading to apoptosis. The molecular chaperone p58(IPK) helps cancer cells survive this metabolic stress.

Area of Science:

  • Oncology
  • Cellular Metabolism
  • Molecular Biology

Background:

  • Solid tumors experience nutrient and oxygen deprivation as they grow.
  • Cellular responses to metabolic stress, particularly glucose shortage, are crucial for malignant progression but remain poorly understood.

Purpose of the Study:

  • To investigate the mechanisms by which malignant cells cope with glucose shortage.
  • To elucidate the role of the endoplasmic reticulum (ER) unfolded protein response (UPR) in tumor growth under metabolic stress.

Main Methods:

  • Utilized a mouse model of K-ras(G12V)-induced lung cancer.
  • Examined the impact of deleting the CHOP gene, a UPR effector.
  • Investigated the role of the molecular chaperone p58(IPK) in regulating the UPR.

Main Results:

  • Glucose shortage triggers apoptosis via the ER unfolded protein response (UPR).
  • Deletion of the proapoptotic UPR effector CHOP increased tumor incidence in a mouse model.
  • The molecular chaperone p58(IPK) attenuates the PERK-CHOP arm of the UPR, enabling cancer cell survival and adaptation.

Conclusions:

  • ER stress acts as a barrier to malignancy, but cancer cells can overcome it.
  • p58(IPK) plays a critical role in allowing malignant cells to adapt to and survive glucose-limiting conditions.
  • ER stress activation and p58(IPK) expression are key determinants of cancer cell fate under metabolic stress.

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