Solid tumours hijack the histone variant network

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. Histone variants are critical for maintenance of genome integrity, nuclear architecture and cell identity. Emerging evidence implicates histone variants and their dedicated chaperones in cancer initiation and progression; this Review examines the key players, their mechanisms of action and strategies to target these therapeutically.

Automated summary

Cancer is a complex disease characterized by loss of cellular homeostasis due to genetic and epigenetic alterations. Histone variants play critical roles in processes like maintenance of genome integrity, nuclear architecture, and cell identity. Cancer cells hijack histone variants and their chaperones to disrupt homeostasis, which is emerging as a common strategy across various cancers, especially solid tumors.