Tasmanian School of Medicine, College of Health and Medicine, University of Tasmania, 17 Liverpool Street, Hobart, TAS, 7000, Australia.
Children's Medical Research Institute, 214 Hawkesbury Road, Westmead, NSW, 2145, Australia.
Oncogene. 2023 Jul;42(31):2363-2373. doi: 10.1038/s41388-023-02773-9. Epub 2023 Jul 11.
The chromatin remodeler SMARCA4/BRG1 is a key epigenetic regulator with diverse roles in coordinating the molecular programs that underlie brain tumour development. BRG1 function in brain cancer is largely specific to the tumour type and varies further between tumour subtypes, highlighting its complexity. Altered SMARCA4 expression has been linked to medulloblastoma, low-grade gliomas such as oligodendroglioma, high-grade gliomas such as glioblastoma and atypical/teratoid rhabdoid tumours. SMARCA4 mutations in brain cancer predominantly occur in the crucial catalytic ATPase domain, which is associated with tumour suppressor activity. However, SMARCA4 is opposingly seen to promote tumourigenesis in the absence of mutation and through overexpression in other brain tumours. This review explores the multifaceted interaction between SMARCA4 and various brain cancer types, highlighting its roles in tumour pathogenesis, the pathways it regulates, and the advances that have been made in understanding the functional relevance of mutations. We discuss developments made in targeting SMARCA4 and the potential to translate these to adjuvant therapies able to enhance current methods of brain cancer treatment.
染色质重塑因子 SMARCA4/BRG1 是一种重要的表观遗传调节剂，在协调脑肿瘤发生的分子程序中具有多种作用。BRG1 在脑癌中的功能在很大程度上是特定于肿瘤类型的，并且在肿瘤亚型之间进一步变化，突出了其复杂性。SMARCA4 表达的改变与髓母细胞瘤、低级别胶质瘤（如少突胶质细胞瘤）、高级别胶质瘤（如胶质母细胞瘤）和非典型/畸胎样横纹肌样肿瘤有关。脑癌中的 SMARCA4 突变主要发生在关键的 ATP 酶催化结构域，这与肿瘤抑制活性有关。然而，在没有突变的情况下，SMARCA4 被认为通过在其他脑肿瘤中过度表达来促进肿瘤发生。本综述探讨了 SMARCA4 与各种脑癌类型之间的多方面相互作用，强调了其在肿瘤发病机制、调节途径以及在理解突变的功能相关性方面取得的进展中的作用。我们讨论了针对 SMARCA4 的进展以及将这些进展转化为辅助治疗的潜力，以增强目前的脑癌治疗方法。
