Cock-Rada, A: Epigenetic Mechanisms of Metastatic Gene Regul

Metastasis is the main cause of mortality due to cancer; therefore, it is crucial to improve our understanding of the regulation of genes controlling the metastatic process in order to develop more effective therapies. Metastasis formation is a multi-step process resulting from genetic and epigenetic alterations in key regulatory molecules. Epigenetic regulatory mechanisms are attractive therapeutic targets as they are potentially reversible. This work focuses on the epigenetic regulation of two metastasis genes, MMP-9 and TIMP-2, in a reversible bovine cancer model induced by Theileria parasites, which allows us to study on-off switches controlling cellular invasion. I found a novel epigenetic regulator of MMP-9, the histone-modifier SMYD3, which also revealed crucial roles in the metastatic properties of human cancer cells. I showed that TIMP-2 is mainly regulated by DNA methylation in Theileria-infected cells, even though other layers of epigenetic control are present on this promoter. This work sheds light on the understanding of epigenetic events controlling metastasis genes, which should be useful for professionals and students interested in cancer genetics.