Related Experiment Video

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Methods to Classify Cytoplasmic Foci as Mammalian Stress Granules
09:33

Methods to Classify Cytoplasmic Foci as Mammalian Stress Granules

Published on: May 12, 2017

Inactivation of the mTORC1-eukaryotic translation initiation factor 4E pathway alters stress granule formation

Marie-Josée Fournier1, Laetitia Coudert, Samia Mellaoui

  • 1Department of Molecular Biology, Laval University, Canada .

Molecular and Cellular Biology
|April 3, 2013
PubMed

Insights

The mTORC1-eIF4E pathway promotes stress granule formation, which inhibits apoptosis and contributes to cancer resistance. Inhibiting this pathway sensitizes cancer cells to death and reduces tumor growth.

Area of Science:

  • Cell Biology
  • Molecular Oncology
  • Cancer Research

Background:

  • Stress granules (SG) are cytoplasmic RNA granules formed under cellular stress.
  • SG inhibit apoptosis, contributing to chemo- and radioresistance in tumors.
  • The involvement of oncogenic signaling in SG formation is largely unknown.

Purpose of the Study:

  • To investigate the role of the mTORC1-eIF4E pathway in stress granule formation.
  • To determine if this pathway influences the antiapoptotic function of SG.
  • To evaluate the therapeutic potential of targeting this pathway in cancer.

Main Methods:

  • Investigated the mechanistic link between mTORC1, eIF4E, and SG formation.
  • Utilized mTOR inhibitor (pp242), eIF4E, and eIF4GI depletion.
  • Assessed the impact on SG-associated antiapoptotic pathways (p21).
  • Evaluated cancer cell death in vitro and tumor growth in vivo.

Main Results:

  • The mTORC1-eIF4E pathway drives SG formation via 4E-BP1 phosphorylation.
  • Disruption of SG formation by pp242, eIF4E, or eIF4GI depletion blocks the antiapoptotic p21 pathway.
  • pp242 treatment sensitizes cancer cells to death and inhibits chemoresistant tumor growth.

Conclusions:

  • The oncogenic mTORC1-eIF4E pathway promotes the formation of antiapoptotic stress granules.
  • Targeting this pathway offers a novel strategy to overcome cancer resistance.
  • Inhibition of mTORC1-eIF4E-mediated SG formation can enhance cancer therapy efficacy.

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