Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Nat Rev Cancer. 2021 Apr;21(4):257-275. doi: 10.1038/s41568-020-00330-0. Epub 2021 Feb 10.
Cancer is a complex disease characterized by loss of cellular homeostasis through genetic and epigenetic alterations. Emerging evidence highlights a role for histone variants and their dedicated chaperones in cancer initiation and progression. Histone variants are involved in processes as diverse as maintenance of genome integrity, nuclear architecture and cell identity. On a molecular level, histone variants add a layer of complexity to the dynamic regulation of transcription, DNA replication and repair, and mitotic chromosome segregation. Because these functions are critical to ensure normal proliferation and maintenance of cellular fate, cancer cells are defined by their capacity to subvert them. Hijacking histone variants and their chaperones is emerging as a common means to disrupt homeostasis across a wide range of cancers, particularly solid tumours. Here we discuss histone variants and histone chaperones as tumour-promoting or tumour-suppressive players in the pathogenesis of cancer.
癌症是一种复杂的疾病，其特征是通过遗传和表观遗传改变导致细胞内稳态丧失。新出现的证据强调了组蛋白变体及其专用伴侣在癌症发生和进展中的作用。组蛋白变体参与了维持基因组完整性、核结构和细胞身份等多种过程。在分子水平上，组蛋白变体为转录、DNA 复制和修复以及有丝分裂染色体分离的动态调控增加了一层复杂性。由于这些功能对于确保正常增殖和维持细胞命运至关重要，因此癌细胞的特征是它们能够颠覆这些功能。劫持组蛋白变体及其伴侣已成为扰乱广泛癌症（尤其是实体瘤）中内稳态的常见手段。在这里，我们将讨论组蛋白变体和组蛋白伴侣作为癌症发病机制中的促进肿瘤或抑制肿瘤的参与者。
