During the Formation of Vasculogenic Mimicry by Melanoma Cells, the Silencing of Two Sets of Developmental Genes Is Coupled Either with an Increase or a Decrease in Contacts with the Nucleoli.

Vasculogenic mimicry is the capacity of growing cancer cells to overcome the lack of normal capillaries and hypoxia by forming networks of sinuses lacking endothelial cells. The formation of vasculogenic mimicry by melanoma cells is coupled with the upregulation of the genes involved in ribosome biogenesis, the downregulation of hundreds of developmental genes, and strong changes in the inter-chromosomal contacts of developmental genes with rDNA clusters. The epigenetic mechanism driving the regulatory role of inter-chromosomal contacts of genes with nucleoli is not yet known. This study aimed to determine whether these contacts are associated with either the silencing or the activation of the expression of developmental genes. Here, two different sets of developmental genes are subjected to silencing either by increasing or decreasing their contacts with nucleoli. Our data indicate that one set of developmental genes mainly associated with system development is silenced by the contacts, while another set of genes involved mainly in the generation of neurons is silenced by the loss of contacts with the nucleoli. We conclude that mechanisms of silencing of these sets of developmental genes lead to the loss of the established differentiated state of melanoma cells and to the formation of more aggressive cancer cells. The data also indicate the important role of the nucleoli in the global regulation of gene expression during differentiation and cancer.