表观遗传可塑性与癌症特征
Epigenetic plasticity and the hallmarks of cancer.
作者信息
Flavahan William A, Gaskell Elizabeth, Bernstein Bradley E
机构信息
Department of Pathology and Center for Cancer Research, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA, and Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
出版信息
Science. 2017 Jul 21;357(6348). doi: 10.1126/science.aal2380.
Chromatin and associated epigenetic mechanisms stabilize gene expression and cellular states while also facilitating appropriate responses to developmental or environmental cues. Genetic, environmental, or metabolic insults can induce overly restrictive or overly permissive epigenetic landscapes that contribute to pathogenesis of cancer and other diseases. Restrictive chromatin states may prevent appropriate induction of tumor suppressor programs or block differentiation. By contrast, permissive or "plastic" states may allow stochastic oncogene activation or nonphysiologic cell fate transitions. Whereas many stochastic events will be inconsequential "passengers," some will confer a fitness advantage to a cell and be selected as "drivers." We review the broad roles played by epigenetic aberrations in tumor initiation and evolution and their potential to give rise to all classic hallmarks of cancer.
染色质及相关的表观遗传机制稳定基因表达和细胞状态，同时也促进对发育或环境信号的适当反应。遗传、环境或代谢损伤可诱导过度受限或过度宽松的表观遗传格局，这有助于癌症和其他疾病的发病机制。受限的染色质状态可能会阻止肿瘤抑制程序的适当诱导或阻断分化。相比之下，宽松或“可塑性”状态可能会允许随机的癌基因激活或非生理性的细胞命运转变。虽然许多随机事件将是无关紧要的“乘客”，但有些将赋予细胞适应性优势并被选为“驱动因素”。我们综述了表观遗传异常在肿瘤起始和演变中所起的广泛作用及其产生癌症所有经典特征的潜力。
Zotero 插件