Spontaneous Immortalization

The model recapitulates the observed time order of spontaneous immortalization phenotypes. Spontaneous immortalization of human epithelial cells proceeds through senescence, EMT-associated senescence escape, and a mesenchymal stem-like tumorigenic phenotype. The nine-node module is sufficient in the model to reproduce the progression from epithelial to senescent to mesenchymal stem-like states. The modeled spontaneous immortalization sequence is linked to inflammation-induced EMT and proposed to parallel phenotype enrichment during carcinoma progression in vivo.