表观遗传学
脱甲基酶
生物
组蛋白
染色质
调节器
癌症研究
转录因子
DNA甲基化
细胞生物学
遗传学
基因表达
基因
作者
M. Weber,Luke Izzo,Trudy G. Oliver
出处
期刊:Cancer Research
[American Association for Cancer Research]
日期:2023-09-26
卷期号:83 (21): 3495-3497
被引量:4
标识
DOI:10.1158/0008-5472.can-23-2922
摘要
Abstract Small-cell lung cancer (SCLC) is a neuroendocrine tumor type with limited treatment options and poor prognosis. SCLC comprises multiple molecular subtypes that are defined by the expression of the lineage-related transcription factors ASCL1, NEUROD1, POU2F3, and more controversially, YAP1. SCLC exhibits remarkable plasticity with the capacity to transition between molecular states; because these states are associated with unique therapeutic susceptibilities, SCLC has been likened to a moving therapeutic target. While MYC's role in driving the ASCL1-to-NEUROD1 (A-to-N) transition is established, additional mechanisms governing SCLC plasticity remain largely obscure. A recent study by Duplaquet and colleagues, published in Nature Cell Biology, employs an innovative genetically engineered mouse model of SCLC harboring loss of KDM6A—a histone lysine demethylase mutated in approximately 2% of SCLC cases. KDM6A loss in SCLC alters chromatin accessibility and increases the potential for A-to-N plasticity in vivo. Through characterization of the epigenetic landscape, Duplaquet and colleagues identified histone methylation as a key regulator of SCLC plasticity. These findings provide not only a new model system for studying SCLC plasticity, but also identify new epigenetic mechanisms involved, which will ultimately be critical for designing more effective therapies.
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