Translation initiation factor 4E confers primary human cells with neoplastic properties

Deregulation of translational control is an obligatory step in oncogenesis; however, this step has not been addressed by prior genomic and transcriptional profiling studies of cancer biology. Here we simulate the translational deregulation found in cancer by ectopically over expressing translation initiation factor eIF4E in primary human mammary epithelial cells; and examine its impact on cell biology and the pattern of ribosomal recruitment to mRNA genome wide. Over expression of eIF4E allows cells to bypass M0 premature growth arrest, but does not confer other malignant properties. However, in concert with hTERT, eIF4E imparts cells with growth and survival autonomy - and profoundly alters the pattern of polyribosome-associated mRNA encoding cell cycle and apoptosis regulators. The translational response to increased eIF4E is not only a unidirectional activation of oncogenic drivers, but also consists of complex intrinsic translational mechanisms that mitigate the acquisition of neoplastic properties.

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Larsson O, Li S, Issaenko OA, Avdulov S, Peterson M, Smith K, Bitterman PB, Polunovsky VA