Nuclear Biophysical Changes during Human Melanoma Plasticity

Abstract

Tumor plasticity is an emerging property of tumor cells which allows them to change their phenotype in dependence on the environment. The epithelial-mesenchymal transition plays a crucial role in helping cells acquire a more aggressive phenotype when they are in the mesenchymal state. Herein, we investigated the biophysical changes occurring during phenotypic switching in human melanoma cells, considering the blebbiness of the nuclei, their stiffness, and the involvement of polycombs with lamins. We show that the formation of cellular heterogeneity involves many crucial nuclear changes including the interaction between different types of polycombs with lamins and chromosome accessibility. Altogether, our results shed new light on the molecular mechanisms involved in the formation of a heterogeneous cell population during phenotypic switching. In particular, our results show that phenotypic switching in melanoma involves chromatin remodeling changing the transcriptional activity of cells and consequently their phenotype.

Keywords: Melanoma; Nuclear morphology; Phenotypic switching.