eIF4E phosphorylation promotes tumorigenesis and is associated with prostate cancer progression

Luc Furic, Liwei Rong, Ola Larsson, Ismael Koumakpayi, Kaori Yoshida, Andrea Brueschke, Emmanuel Petroulakis, Nathaniel Robichaud, Michael Pollak, Louis Gaboury, Pier Pandolfi, Fred Saad, N Sonenberg

Research output: Contribution to journalArticleResearchpeer-review

327 Citations (Scopus)

Abstract

Translational regulation plays a critical role in the control of cell growth and proliferation. A key player in translational control is eIF4E, the mRNA 5 cap-binding protein. Aberrant expression of eIF4E promotes tumorigenesis and has been implicated in cancer development and progression. The activity of eIF4E is dysregulated in cancer. Regulation of eIF4E is partly achieved through phosphorylation. However, the physiological significance of eIF4E phosphorylation in mammals is not clear. Here, we show that knock-in mice expressing a nonphosphorylatable form of eIF4E are resistant to tumorigenesis in a prostate cancer model. By using a genome-wide analysis of translated mRNAs, we show that the phosphorylation of eIF4E is required for translational up-regulation of several proteins implicated in tumorigenesis. Accordingly, increased phospho-eIF4E levels correlate with disease progression in patients with prostate cancer. Our findings establish eIF4E phosphorylation as a critical event in tumorigenesis. These findings raise the possibility that chemical compounds that prevent the phosphorylation of eIF4E could act as anticancer drugs.
Original languageEnglish
Pages (from-to)14134 - 14139
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume107
Issue number32
DOIs
Publication statusPublished - 2010
Externally publishedYes

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