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Updated: Mar 13, 2026
Monitoring eIF4F Assembly by Measuring eIF4E-eIF4G Interaction in Live Cells
Published on: May 1, 2020
Molecular Pathways: The eIF4F Translation Initiation Complex-New Opportunities for Cancer Treatment
Hélène Malka-Mahieu1,2,3, Michelle Newman1,2,3, Laurent Désaubry4,5
1Institut Curie, PSL Research University, CNRS UMR 3348, Orsay, France.
Abstract:
The eIF4F complex regulates the cap-dependent mRNA translation process. It is becoming increasingly evident that aberrant activity of this complex is observed in many cancers, leading to the selective synthesis of proteins involved in tumor growth and metastasis. The selective translation of cellular mRNAs controlled by this complex also contributes to resistance to cancer treatments, and downregulation of the eIF4F complex components can restore sensitivity to various cancer therapies. Here, we review the contribution of the eIF4F complex to tumorigenesis, with a focus on its role in chemoresistance as well as the promising use of new small-molecule inhibitors of the complex, including flavaglines/rocaglates, hippuristanol, and pateamine A. Clin Cancer Res; 23(1); 21-25. ©2016 AACR.
Insights
Aberrant activity of the eukaryotic initiation factor 4F (eIF4F) complex drives cancer growth and treatment resistance. Inhibiting this complex shows promise for restoring cancer therapy sensitivity.
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- The eukaryotic initiation factor 4F (eIF4F) complex is crucial for cap-dependent mRNA translation.
- Aberrant eIF4F activity is implicated in various cancers, promoting tumor growth and metastasis.
- This complex's role in selective protein synthesis contributes to cancer treatment resistance.
Purpose of the Study:
- To review the role of the eIF4F complex in tumorigenesis.
- To focus on the eIF4F complex's contribution to chemoresistance.
- To discuss novel small-molecule inhibitors targeting the eIF4F complex.
Main Methods:
- Literature review of the eIF4F complex in cancer.
- Analysis of eIF4F's role in chemoresistance mechanisms.
- Examination of small-molecule inhibitors like flavaglines/rocaglates, hippuristanol, and pateamine A.
Main Results:
- The eIF4F complex selectively synthesizes proteins that drive tumor progression.
- Dysregulation of eIF4F contributes significantly to resistance against cancer therapies.
- Downregulation of eIF4F components can re-sensitize cancer cells to treatments.
Conclusions:
- The eIF4F complex is a key player in cancer development and therapeutic resistance.
- Targeting the eIF4F complex with small-molecule inhibitors is a promising therapeutic strategy.
- Inhibitors such as flavaglines/rocaglates, hippuristanol, and pateamine A warrant further investigation.
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