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Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
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Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells

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Overexpression of phospho-eIF4E is associated with survival through AKT pathway in non-small cell lung cancer

Akihiko Yoshizawa1, Junya Fukuoka, Shigeki Shimizu

  • 1Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|December 17, 2009
PubMed
Abstract

Insights

Phosphorylated eukaryotic translation initiation factor 4E (p-eIF4E) and phosphorylated AKT (p-AKT) overexpression in non-small cell lung cancer (NSCLC) indicates a poor prognosis. Their combined presence significantly shortens survival, highlighting eIF4E

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The mammalian target of rapamycin (mTOR) pathway regulates cell growth and is often dysregulated in cancer.
  • Eukaryotic translation initiation factor 4E (eIF4E) is a key regulator of cap-dependent translation and is downstream of mTOR.
  • Aberrant activation of signaling pathways, including PTEN/AKT and RAS/MEK/ERK, is common in non-small cell lung carcinoma (NSCLC).

Purpose of the Study:

  • To investigate the expression of eIF4E and its phosphorylated form (p-eIF4E) in NSCLC.
  • To determine the relationship between p-eIF4E expression and the PTEN/AKT and RAS/MEK/ERK signaling pathways.
  • To evaluate the prognostic significance of p-eIF4E and related pathway markers in NSCLC patients.

Main Methods:

  • Immunohistochemical analysis was performed on a tissue microarray of 300 NSCLC tumors.
  • Expression levels of p-eIF4E, p-AKT, PTEN, p-TSC2, p-mTOR, p-S6, and p-Erk1/2 were assessed.
  • Staining results were correlated with clinical-pathologic features and survival data.

Main Results:

  • Overexpression of p-eIF4E was observed in 39.9% of NSCLC tumors.
  • p-eIF4E expression positively correlated with p-AKT, p-TSC2, and p-S6.
  • Overexpression of p-eIF4E and/or p-AKT was associated with significantly shorter overall survival in NSCLC patients.
  • Multivariate analysis identified p-eIF4E overexpression as an independent prognostic factor for NSCLC.

Conclusions:

  • Phosphorylated eIF4E (p-eIF4E) expression, particularly in conjunction with p-AKT, is a predictor of poor prognosis in NSCLC.
  • The correlation between p-eIF4E and markers of the AKT pathway (p-AKT, p-TSC2, p-S6) suggests a crucial role for eIF4E activation via AKT in NSCLC progression.

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