title: eIF4E phosphorylation promotes tumorigenesis and is associated with prostate cancer progression.
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.
authors.affiliation: Goodman Cancer Centre and Department of Biochemistry, Cancer Pavilion, McGill University, Montreal, QC, Canada H3A 1A3. luc.furic@mcgill.ca
authors.forename: Luc
authors.initials: L
authors.lastname: Furic
authors.forename: Liwei
authors.initials: L
authors.lastname: Rong
authors.forename: Ola
authors.initials: O
authors.lastname: Larsson
authors.forename: Ismaël Hervé
authors.initials: IH
authors.lastname: Koumakpayi
authors.forename: Kaori
authors.initials: K
authors.lastname: Yoshida
authors.forename: Andrea
authors.initials: A
authors.lastname: Brueschke
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Petroulakis
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Robichaud
authors.forename: Michael
authors.initials: M
authors.lastname: Pollak
authors.forename: Louis A
authors.initials: LA
authors.lastname: Gaboury
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Pandolfi
authors.forename: Fred
authors.initials: F
authors.lastname: Saad
authors.forename: Nahum
authors.initials: N
authors.lastname: Sonenberg
mesh_terms: D000818:Animals; D018450:Disease Progression; D039561:Eukaryotic Initiation Factor-4E / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D055879:Gene Knock-In Techniques; D006801:Humans; D008297:Male; D051379:Mice; D009363:Neoplasm Proteins / Q000235:genetics; D009369:Neoplasms / Q000209:etiology* / Q000235:genetics / Q000473:pathology*; D010766:Phosphorylation / Q000502:physiology; D015854:Up-Regulation
chemical_list: D039561:Eukaryotic Initiation Factor-4E; D009363:Neoplasm Proteins