Author : Dimitrios Karagiannis
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (139 download)
Book Synopsis Epigenetic Targeting of Metabolic and Lineage Abnormality in Cancer by : Dimitrios Karagiannis
Download or read book Epigenetic Targeting of Metabolic and Lineage Abnormality in Cancer written by Dimitrios Karagiannis and published by . This book was released on 2023 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Specifically, we employed a chromatin-focused genetic screen to identify dependencies on chromatin regulators. The screen revealed an NRF2-specific dependency on class I histone deacetylases. Experiments in mouse and human LUAD cell lines in vitro and in vivo indicated an NRF2-specific sensitivity to the class I HDAC inhibitor Romidepsin. Mechanistically, profiling of histone acetylation and gene expression upon Romidepsin treatment revealed a relative loss of histone H4 acetylation at promoters which was associated with reduced gene expression. Many downregulated genes were more essential for the survival of NRF2 hyperactive cancer cells, including genes involved in glutamine and serine metabolism, c-Myc and several of its targets involved in purine and pyrimidine synthesis. These transcriptional changes had corresponding effects on altering the metabolic pathways that NRF2-active cells selectively require for survival. In the study on neuroendocrine esophageal carcinoma (NEC), we identified a crucial role for epigenetic regulation of lineage fate through transcriptional control of the key epidermal transcription factor p63.