1. Strong Activation of ID1 , ID2 , and ID3 Genes Is Coupled with the Formation of Vasculogenic Mimicry Phenotype in Melanoma Cells.
- Author
-
Tchurikov NA, Vartanian AA, Klushevskaya ES, Alembekov IR, Kretova AN, Lukicheva VN, Chechetkin VR, Kravatskaya GI, Kosorukov VS, and Kravatsky YV
- Subjects
- Humans, Cell Line, Tumor, Neovascularization, Pathologic genetics, Neovascularization, Pathologic metabolism, Phenotype, Cell Differentiation genetics, Epigenesis, Genetic, Drug Combinations, Collagen, Proteoglycans, Laminin, Neoplasm Proteins, Melanoma genetics, Melanoma pathology, Melanoma metabolism, Inhibitor of Differentiation Proteins genetics, Inhibitor of Differentiation Proteins metabolism, Gene Expression Regulation, Neoplastic, Inhibitor of Differentiation Protein 2 genetics, Inhibitor of Differentiation Protein 2 metabolism, Inhibitor of Differentiation Protein 1 genetics, Inhibitor of Differentiation Protein 1 metabolism
- Abstract
Gene expression patterns are very sensitive to external influences and are reflected in phenotypic changes. It was previously described that transferring melanoma cells from a plastic surface to Matrigel led to formation of de novo vascular networks-vasculogenic mimicry-that are characteristic to a stemness phenotype in aggressive tumors. Up to now there was no detailed data about the gene signature accompanying this process. Here, we show that this transfer shortly led to extremely strong epigenetic changes in gene expression in the melanoma cells. We observed that on Matrigel numerous genes controlling ribosome biogenesis were upregulated. However, most of the activated genes were inhibitors of the differentiation genes ( ID1 , ID2 , and ID3 ). At the same time, the genes that control differentiation were downregulated. Both the upregulated and the downregulated genes are simultaneously targeted by different transcription factors shaping sets of co-expressed genes. The specific group of downregulated genes shaping contacts with rDNA genes are also associated with the H3K27me3 mark and with numerous lincRNAs and miRNAs. We conclude that the stemness phenotype of melanoma cells is due to the downregulation of developmental genes and formation of dedifferentiated cells.
- Published
- 2024
- Full Text
- View/download PDF