Canu Valeria, Blandino Giovanni
Translational Oncology Research Unit, IRCCS Regina Elena National Cancer Institute, Via Elio Chianesi 53, 00144, Rome, Italy.
Dig Dis Sci. 2025 Sep 19. doi: 10.1007/s10620-025-09401-4.
YEATS domain-containing proteins (ENL, AF9, YEATS2, YEATS4) have emerged as key chromatin readers that recognize histone acylation marks to regulate transcription, chromatin accessibility, and DNA repair. In their recent review, Fu et al. delineate the diverse oncogenic functions of YEATS paralogs across digestive system malignancies, emphasizing their roles in integrating chromatin dynamics with signaling pathways such as PI3K/AKT, Wnt/β-catenin, HIF1α, and c-Myc. Although the structural features of YEATS domains pose challenges for pharmacological targeting, their consistent involvement in oncogenic transcriptional programs highlights them as promising epigenetic targets. This commentary critically appraises the review's contribution, highlighting its mechanistic breadth and the implications for targeting YEATS proteins in gastrointestinal tumors.
含YEATS结构域的蛋白质（ENL、AF9、YEATS2、YEATS4）已成为关键的染色质读取蛋白，可识别组蛋白酰化标记以调节转录、染色质可及性和DNA修复。在他们最近的综述中，傅等人阐述了YEATS旁系同源物在消化系统恶性肿瘤中的多种致癌功能，强调了它们在将染色质动力学与PI3K/AKT、Wnt/β-连环蛋白、HIF1α和c-Myc等信号通路整合中的作用。尽管YEATS结构域的结构特征对药物靶向提出了挑战，但它们在致癌转录程序中的持续参与突出了它们作为有前景的表观遗传靶点的地位。本评论批判性地评估了该综述的贡献，强调了其机制的广度以及靶向YEATS蛋白在胃肠道肿瘤中的意义。
