DNA Methylation, Epigenetics and Metastasis

Most of the cancer patients die because the tumoral cells do not "stick" in the original site, but instead detach, invade and disseminate throughout the bloodstream to distal sites, where these transformed cells start to proliferate and destroy again. In the last ten years, researchers have identified a number of important genes involved in these processes, including cadherins, laminins, heparan sulfates, inhibitors of proteases and angiogenesis and many others. The puzzling problem was that few genetic alterations in these genes had been described in human tumors, despite the common finding of down-regulation. CpG island hypermethylation-associated silencing has come to the rescue of several of these genes and has situated them in the forefront of the current cancer research. However epigenetic silencing is also much more than aberrant DNA methylation, a whole set of histone modifiers and chromatin remodelling factors "conspire" to maintain the repression of these tumor/metastasis suppressor genes. DNA demethylating agents and inhibitors of histone deacetylases are the first generation of epigenetic drugs to beat them. In this book, the current directions in the epigenetics of cancer progression and metastasis are comprehensively described. It is now the turn of the reader to take care of the future. Dr Manel Esteller, Director, Cancer Epigenetics Laboratory, Spanish National Cancer Centre (CNIO) mesteller@cnio.

Résumé
Most of the cancer patients die because the tumoral cells do not stick in the original site, but instead detach, invade and disseminate throughout the bloodstream to distal sites, where these transformed cells start to proliferate and destroy again. In the last ten years, researchers have identified a number of important genes involved in these processes, including cadherins, laminins, heparan sulfates, inhibitors of proteases and angiogenesis and many others. The puzzling problem was that few genetic alterations in these genes had been described in human tumors, despite the common finding of down-regulation. CpG island hypermethylation-associated silencing has come to the rescue of several of these genes and has situated them in the forefront of the current cancer research. However epigenetic silencing is also much more than aberrant DNA methylation, a whole set of histone modifiers and chromatin remodelling factors conspire to maintain the repression of these tumor/metastasis suppressor genes. DNA demethylating agents and inhibitors of histone deacetylases are the first generation of epigenetic drugs to beat them. In this book, the current directions in the epigenetics of cancer progression and metastasis are comprehensively described. It is now the turn of the reader to take care of the future. Dr Manel Esteller, Director, Cancer Epigenetics Laboratory, Spanish National Cancer Centre (CNIO) mesteller@cnio.

Contenu

How CpG Island Hypermethylation Leads to Cancer Dissemination: The Sounds of Silence for Tumor and Metastasis Suppressor Genes.- A Mouse Skin Multistage Carcinogenesis Model That Unmasks Epigenetic Lesions Responsible for Metastasis.- CpG Island Hypermethylation and Lung Cancer Invasion and Metastasis.- CpG Island Hypermethylation Changes during Prostate Cancer Progression and Metastasis.- CpG Island Hypermethylation in Breast Cancer Progression and Metastasis.- Epigenetic Dysregulation of Maspin (SerpinB5) in Cancer Invasion and Metastasis.- Epigenetic Regulation of the E-Cadherin Cell-Cell Adhesion Gene.- Epigenetic Disruption of the SLIT-ROBO Interactions in Human Cancer.- Molecular Mechanisms of the Metastasis-Associated Gene Family of Coregulators: Role in Cancer and Invasion.- The Molecular Mechanisms for Breast Cancer Metastasis Suppressor 1 Action in Cancer Metastasis.- Mechanisms of DNA Demethylating Drugs Against Cancer Progression.- Histone Deacetylase Inhibitors: Novel Targeted Anti-Cancer Agents.