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Published on: September 27, 2015
Initiation of mRNA translation in oncogenesis: the role of eIF4E
Lorenzo Montanaro1, Pier Paolo Pandolfi
1Cancer Biology and Genetics Program, Department of Pathology, Sloan-Kettering Institute, Memorial Sloan-Kettering Cancer Center,New York, New, York 10021, USA.
Abstract:
The eukaryotic initiation factor 4E (eIF4E) is a key regulator of protein translation whose function is activated by the Akt and Ras proto-oncogenic signal transduction pathways. eIF4E enhances the translation of mRNAs encoding several genes involved in tumorigenesis and acts as a proto-oncogene, in vitro, when overexpressed in immortalized cells. Importantly, eIF4E is frequently found overexpressed in human cancers of multiple histological origins. However, in vivo evidence of the eIF4E neoplastic potential was lacking until now. Here we discuss recent findings that demonstrate eIF4E's oncogenic role in vivo through direct genetic approaches in the mouse, and identify novel oncogenic functions for this initiation factor in cooperative tumorigenesis and response to therapy.
Insights
Eukaryotic initiation factor 4E (eIF4E) drives cancer in vivo. New research shows eIF4E
Area of Science:
- Molecular Biology
- Oncology
- Biochemistry
Background:
- Eukaryotic initiation factor 4E (eIF4E) is a key regulator of protein translation.
- eIF4E is frequently overexpressed in human cancers and acts as a proto-oncogene in vitro.
- In vivo evidence for eIF4E's oncogenic potential was previously lacking.
Purpose of the Study:
- To demonstrate the in vivo oncogenic role of eIF4E.
- To identify novel oncogenic functions of eIF4E in tumorigenesis and therapy response.
Main Methods:
- Direct genetic approaches in mouse models.
- Analysis of tumorigenesis and response to therapy.
Main Results:
- Demonstrated eIF4E's oncogenic role in vivo.
- Identified novel functions in cooperative tumorigenesis.
- Revealed eIF4E's role in response to therapy.
Conclusions:
- eIF4E possesses an in vivo oncogenic role.
- eIF4E contributes to cooperative tumorigenesis.
- eIF4E influences response to cancer therapy.
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01:31Translation
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