eIF4E-mediated translational control of cancer incidence.

Mitogen activated translation initiation factor eIF4E mediates normal cell proliferation, yet induces tumorigenesis when deregulated and overexpressed. It remains unknown, how activated eIF4E directs such distinct biological outputs. Our experimental data provide evidence that distinct threshold levels of eIF4E govern its biological output in lactating mammary glands and that eIF4E overexpression in the context of cell population expansion can initiate malignant transformation by enabling cells to evade DNA damage checkpoints caused by hyperproliferative oncogenic stimuli. These findings point at the cellular level of eIF4E as an important sensor for normal or pro-neoplastic propagation of cells. Here, we describe a model that links the pro-neoplastic function of eIF4F to its ability to disable oncogene-activated tumor surveillance programs; and propose a novel therapeutic strategy for cancer prevention based upon targeting aberrant eIF4E with safe doses of small-molecule antagonists to ensure the maintenance of eIF4E levels below the pro-neoplastic threshold. This article is part of a Special Issue entitled: Translation and Cancer. Published by Elsevier B.V.