Li Haoyan, Gigi Loraine, Zhao Di
Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, United States.
Texas A&M School of Public Health, Texas A&M University, College Station, TX, United States.
Front Oncol. 2023 Jan 26;13:1123362. doi: 10.3389/fonc.2023.1123362. eCollection 2023.
Chromatin remodeling proteins contribute to DNA replication, transcription, repair, and recombination. The chromodomain helicase DNA-binding (CHD) family of remodelers plays crucial roles in embryonic development, hematopoiesis, and neurogenesis. As the founding member, CHD1 is capable of assembling nucleosomes, remodeling chromatin structure, and regulating gene transcription. Dysregulation of CHD1 at genetic, epigenetic, and post-translational levels is common in malignancies and other human diseases. Through interacting with different genetic alterations, CHD1 possesses the capabilities to exert oncogenic or tumor-suppressive functions in context-dependent manners. In this Review, we summarize the biochemical properties and dysregulation of CHD1 in cancer cells, and then discuss CHD1's roles in different contexts of prostate cancer, with an emphasis on its crosstalk with diverse signaling pathways. Furthermore, we highlight the potential therapeutic strategies for cancers with dysregulated CHD1. At last, we discuss current research gaps in understanding CHD1's biological functions and molecular basis during disease progression, as well as the modeling systems for biology study and therapeutic development.
染色质重塑蛋白参与DNA复制、转录、修复和重组过程。染色质结构域解旋酶DNA结合(CHD)家族的重塑蛋白在胚胎发育、造血作用和神经发生中发挥关键作用。作为该家族的创始成员,CHD1能够组装核小体、重塑染色质结构并调节基因转录。在恶性肿瘤和其他人类疾病中,CHD1在基因、表观遗传和翻译后水平的失调很常见。通过与不同的基因改变相互作用,CHD1能够以依赖于背景的方式发挥致癌或肿瘤抑制功能。在本综述中,我们总结了癌细胞中CHD1的生化特性和失调情况,然后讨论CHD1在前列腺癌不同背景下的作用,重点是其与多种信号通路的相互作用。此外,我们强调了针对CHD1失调癌症的潜在治疗策略。最后,我们讨论了目前在理解CHD1在疾病进展过程中的生物学功能和分子基础方面的研究空白,以及用于生物学研究和治疗开发的建模系统。