Phosphorylation of eIF4E promotes EMT and metastasis via translational control of SNAIL and MMP-3

N Robichaud1, S V del Rincon2, B Huor2

  • 1Department of Biochemistry and Goodman Cancer Research Centre, McGill University, Montreal, Quebec, Canada.

Oncogene
|June 10, 2014
PubMed

Insights

Phosphorylation of eukaryotic translation initiation factor 4E (eIF4E) drives cancer metastasis. Inhibiting eIF4E phosphorylation prevents lung metastases and impairs invasion, revealing a key role in cancer progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Cancer metastasis is a major cause of mortality.
  • Translational control, particularly involving eukaryotic translation initiation factor 4E (eIF4E), is crucial in cancer.
  • The role of eIF4E phosphorylation in metastasis remains unclear.

Purpose of the Study:

  • To investigate the role of eIF4E phosphorylation in cancer metastasis.
  • To elucidate the mechanisms by which eIF4E phosphorylation influences invasion and epithelial-to-mesenchymal transition (EMT).

Main Methods:

  • Utilized a mouse mammary tumor model to assess lung metastasis.
  • Analyzed isolated cells for invasion capabilities.
  • Investigated the effect of transforming growth factor-beta (TGFβ) on eIF4E phosphorylation and target mRNA translation.
  • Examined the role of eIF4E phosphorylation in TGFβ-induced EMT.

Main Results:

  • Mice with non-phosphorylatable eIF4E were resistant to lung metastases.
  • Cells lacking eIF4E phosphorylation showed impaired invasion.
  • TGFβ induces eIF4E phosphorylation, enhancing translation of Snail and Mmp-3 mRNAs.
  • TGFβ-induced EMT requires eIF4E phosphorylation via a non-canonical signaling pathway.

Conclusions:

  • eIF4E phosphorylation is essential for cancer metastasis.
  • Targeting eIF4E phosphorylation may offer a therapeutic strategy against cancer spread.
  • A novel model highlights the role of eIF4E phosphorylation in TGFβ-induced EMT and metastasis.

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