Transformed cells after senescence give rise to more severe tumor phenotypes than transformed non-senescent cells

Oncogenic stress-induced senescence initially inhibits tumor initiation by blocking proliferation. If these cells are not eliminated they may resume proliferation upon loss-of-tumor suppressors, and be at risk of transformation. During tumor formation, depending on the sequence of events of gain-of-oncogenes and/or loss-of-tumor suppressors, cancer cells may emerge from senescent cells. The goal of this study is to determine if transformed cells after senescence (TS) display more aggressive tumorigenic features, with a greater capacity to migrate and a higher resistance to anti-tumoral drugs than cells having undergone transformation without senescence. Here, we modeled cell transformation using mouse embryonic fibroblasts (MEFs) subjected to an inverse sequence of events: i) gain-of-RasV12 oncogene and loss-of-p53 tumor suppressor, leading to transformed cells after senescence (TS), or ii) the opposite, resulting in transformed (T) non-senescent cells. This study is based on transciptome analysis of Mouse Embrionic Fibroblasts (MEFs) expressing 4 different combination of viral vectors: Oncogenic form of RAS (RASV12); short hairpin RNA targeting mouse p53 mRNA (shp53); first shp53 plus RASV12 (T cells); or first RASV12 plus shp53 (TS cells) .For each condition three independent biological replicates were analysed.