Xu Shouying, Tang Chao
National Clinical Research Center for Child Health of the Children's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Front Oncol. 2021 Oct 4;11:745187. doi: 10.3389/fonc.2021.745187. eCollection 2021.
Genes encoding subunits of SWItch/Sucrose Non-Fermenting (SWI/SNF) chromatin remodeling complexes are collectively mutated in 20% of all human cancers, among which the (, also known as , , , ) that encodes protein ARID1A is the most frequently mutated, and mutations in have been found in various types of cancer. ARID1A is thought to play a significant role both in tumor initiation and in tumor suppression, which is highly dependent upon context. Recent molecular mechanistic research has revealed that ARID1A participates in tumor progression through its effects on control of cell cycle, modulation of cellular functions such as EMT, and regulation of various signaling pathways. In this review, we synthesize a mechanistic understanding of the role of in human tumor initiation as well as in tumor suppression and further discuss the implications of these new discoveries for potential cancer intervention. We also highlight the mechanisms by which mutations affecting the subunits in SWI/SNF complexes promote cancer.
编码SWItch/蔗糖非发酵(SWI/SNF)染色质重塑复合物亚基的基因在所有人类癌症中总体突变率为20%,其中编码蛋白ARID1A的基因(也称为、、、)是最常发生突变的,并且在各种类型的癌症中均发现了该基因的突变。ARID1A被认为在肿瘤起始和肿瘤抑制中均发挥重要作用,这高度依赖于具体情况。最近的分子机制研究表明,ARID1A通过影响细胞周期控制、调节如上皮-间质转化等细胞功能以及调控各种信号通路来参与肿瘤进展。在本综述中,我们综合了对ARID1A在人类肿瘤起始以及肿瘤抑制中作用的机制理解,并进一步讨论了这些新发现对潜在癌症干预的意义。我们还强调了影响SWI/SNF复合物亚基的突变促进癌症的机制。