CNRS, EMR9002 Integrative Structural Biology, F-59000 Lille, France.
Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1167-RID-AGE-Risk Factors and Molecular Deter-minants of Aging-Related Diseases, F-59000 Lille, France.
Int J Mol Sci. 2023 Aug 30;24(17):13454. doi: 10.3390/ijms241713454.
ETS transcription factors are a highly conserved family of proteins involved in the progression of many cancers, such as breast and prostate carcinomas, Ewing's sarcoma, and leukaemias. This significant involvement can be explained by their roles at all stages of carcinogenesis progression. Generally, their expression in tumours is associated with a poor prognosis and an aggressive phenotype. Until now, no efficient therapeutic strategy had emerged to specifically target ETS-expressing tumours. Nevertheless, there is evidence that pharmacological inhibition of poly(ADP-ribose) polymerase-1 (PARP-1), a key DNA repair enzyme, specifically sensitises ETS-expressing cancer cells to DNA damage and limits tumour progression by leading some of the cancer cells to death. These effects result from a strong interplay between ETS transcription factors and the PARP-1 enzyme. This review summarises the existing knowledge of this molecular interaction and discusses the promising therapeutic applications.
ETS 转录因子是一类高度保守的蛋白家族，参与多种癌症的进展，如乳腺癌、前列腺癌、尤因肉瘤和白血病。它们在致癌过程的所有阶段都发挥作用，这可以解释其重要的参与作用。通常，肿瘤中这些因子的表达与预后不良和侵袭性表型相关。到目前为止，还没有出现专门针对表达 ETS 的肿瘤的有效治疗策略。然而，有证据表明，药理学抑制多聚（ADP-核糖）聚合酶-1（PARP-1），一种关键的 DNA 修复酶，可特异性地使表达 ETS 的癌细胞对 DNA 损伤敏感，并通过导致部分癌细胞死亡来限制肿瘤的进展。这些效应源自 ETS 转录因子和 PARP-1 酶之间的强烈相互作用。本文综述了这一分子相互作用的现有知识，并讨论了其有前景的治疗应用。
