Epigenetics as a mediator of plasticity in cancer

• 成果类型: Review
• 署名作者: Feinberg, Andrew P.; Levchenko, Andre
• 署名单位: Johns Hopkins University; Johns Hopkins University; Johns Hopkins University; Yale University; Yale University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-9898
• DOI: 10.1126/science.aaw3835
• 发表日期: 2023-02-10
• 页码: 552-+
• 关键词: tumor-suppressor gene; dna methylation; information-transmission; cell plasticity; Heterogeneity; landscape; mutations; noise; drift; hydroxymethylation

摘要

The concept of an epigenetic landscape describing potential cellular fates arising from pluripotent cells, first advanced by Conrad Waddington, has evolved in light of experiments showing nondeterministic outcomes of regulatory processes and mathematical methods for quantifying stochasticity. In this Review, we discuss modern approaches to epigenetic and gene regulation landscapes and the associated ideas of entropy and attractor states, illustrating how their definitions are both more precise and relevant to understanding cancer etiology and the plasticity of cancerous states. We address the interplay between different types of regulatory landscapes and how their changes underlie cancer progression. We also consider the roles of cellular aging and intrinsic and extrinsic stimuli in modulating cellular states and how landscape alterations can be quantitatively mapped onto phenotypic outcomes and thereby used in therapy development.