Genome reprogramming in cells that escape from senescence

Xavier Deschênes-Simard; Stéphane Roy; Gerardo Ferbeyre

Genome reprogramming in cells that escape from senescence

2016

Xavier Deschênes-Simard | Stéphane Roy | Gerardo Ferbeyre

Many tumorigenic stimuli trigger a protective cellular response known as cellular senescence, a stable cell cycle arrest characterized by an active metabolism, secretion of immunomodulatory factors and activation of tumor suppressor pathways. The senescence state depends on the continuous and aberrant activation of signalling pathways. Senescent cells will remain non-dividing as long as this aberrant signalling is maintained. However, if these signals are attenuated, senescent cells can escape form their dormant condition and dangerously progress into tumor formation. Here we compare the transcriptome of oncogenic Ras–induced senescent cells with that of cells that escaped from senescence after attenuation of the ERK/MAP kinase signaling pathway. We found that cells that escaped from senescence express genes associated to genetic instability and display a highly aberrant karyotype. These cells also express genes commonly altered in the cancer transcriptome of different tissues supporting the idea of a common gene expression program that governs cancer cells. Bioinformatic analyses identified the transcription factors most likely regulating the gene expression programs of senescent cells and cells that escape from senescence. We propose a model of carcinogenesis where cells that escape from senescence provide a heterogeneous population of genetically unstable cells that can progress into malignant tumors.

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