Abdalla Shaima, Forghany Zary, Ma Jin, Hollander Johan G, Nachane Ruta, Szuhai Karoly, Hogendoorn Pancras C W, Ten Dijke Peter, Shah Dipen, Baker David A
Oncode Institute and Department of Cell & Chemical Biology, Leiden University Medical Center (LUMC), The Netherlands.
ZoBio BV, Leiden, The Netherlands.
FEBS Lett. 2025 Jun;599(12):1733-1748. doi: 10.1002/1873-3468.70040. Epub 2025 Apr 11.
The evolutionarily conserved E-Twenty-Six (ETS) family of transcription factors acts downstream of major signal transduction pathways and plays a pivotal role in tissue development and maintenance. Importantly, their function is frequently corrupted in a substantial proportion of tumour types, and they are also indispensable for angiogenic sprouting, a hallmark of cancer, which is essential for fuelling tumour enlargement and dissemination. Consequently, targeting aberrant ETS activity could potentially represent a precise and effective means by which to block tumour growth. Here, we present proof-of-principle high-throughput screens and an initial characterization of candidate hits, as a methodological and conceptual framework for the identification of novel ETS transcription factor inhibitors, which may ultimately lead to new therapeutic avenues for treating cancer.
进化上保守的E-26（ETS）转录因子家族在主要信号转导通路的下游发挥作用，在组织发育和维持中起关键作用。重要的是，它们的功能在相当一部分肿瘤类型中经常受损，并且它们对于血管生成芽生（癌症的一个标志，对促进肿瘤扩大和扩散至关重要）也是不可或缺的。因此，靶向异常的ETS活性可能是一种精确有效的阻断肿瘤生长的方法。在这里，我们展示了原理验证高通量筛选以及候选命中物的初步表征，作为鉴定新型ETS转录因子抑制剂的方法学和概念框架，这最终可能会为癌症治疗带来新的治疗途径。
