John Samu, Kalathil Dhanya, Pothuraju Ramesh, Nair Sivakumari Asha
Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695014, India; Research Centre, University of Kerala, Thiruvananthapuram 695034, India; Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico, Albuquerque, NM 87131, USA.
Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695014, India; Department of Biology, Morrissey College of Arts and Sciences, Boston College, Chestnut Hill, MA 02467, USA.
Biochim Biophys Acta Rev Cancer. 2025 Sep;1880(4):189368. doi: 10.1016/j.bbcan.2025.189368. Epub 2025 Jun 7.
E26 Transformation-Specific homolog 2 (ETS2) is a founding member of the ETS family of transcription factors and has been implicated in several developmental and survival functions. The predominant route of its action is by directly binding and regulating the promoters of its target genes, although it can function through other regulatory mechanisms as well. In this review, a comprehensive understanding of the contribution of ETS2 in health and disease is described with specific focus on cancer. ETS2 demonstrates extreme complexity as it can act as a double-edged sword in cancer with tumour suppressive or oncogenic functions in a context specific manner. Here, we delineate the different signalling pathways, post-translational modifications, miRNA regulations and protein-protein interactions that illustrate the role of ETS2 as an emerging biomarker with special emphasis on its contribution to 'hallmarks of cancer'. Given the evidently opposing effects of ETS2 in different cancers, elucidating the critical mechanisms in its development and progression can validate ETS2's potential as a novel therapeutic target. Finally, we provide insights into frontier areas of research focus that implicate ETS2 and can translate into clinical outcomes.
E26转化特异性同源物2（ETS2）是ETS转录因子家族的创始成员，参与多种发育和生存功能。其主要作用途径是直接结合并调控靶基因的启动子，不过它也可通过其他调控机制发挥作用。在本综述中，我们描述了对ETS2在健康和疾病中的作用的全面理解，特别关注癌症方面。ETS2表现出极端的复杂性，因为它在癌症中可作为一把双刃剑，在特定背景下具有肿瘤抑制或致癌功能。在此，我们阐述了不同的信号通路、翻译后修饰、miRNA调控和蛋白质-蛋白质相互作用，这些说明了ETS2作为一种新兴生物标志物的作用，特别强调了其对“癌症特征”的贡献。鉴于ETS2在不同癌症中具有明显相反的作用，阐明其在癌症发生和发展中的关键机制可以验证ETS2作为新型治疗靶点的潜力。最后，我们提供了对涉及ETS2且可转化为临床结果的前沿研究重点领域的见解。
