An epigenetic mechanism underlying melanoma cancer metastasis persistence

In this work, we build a computational dynamical system model to recapitulate a recent experimental finding of melanoma cancer metastasis persistence under the induction of the Notch pathway. We found that the regulatory feedback at the histone level could be a potential contributor to such persistence of the metastatic phenotype. Furthermore, we studied how different types of Notch ligand dynamics affect the underlying epigenetic states, thus leading to different cell fates. Furthermore, a 1D Duffing oscillator is used to theoretically understand the relationship between the phenotypic switching amplitude and switching frequency at the histone level.