Corrupted devolution: How normal cells are reborn as cancer precursors. (August 2022)

• Record Type: Journal Article
• Authors: Lord, Alice; Ficz, Gabriella
• Is Part Of: International journal of biochemistry & cell biology. Volume 149(2022)
• Publication Date: 2022-08
• Subjects: Dedifferentiation -- Embryogenesis -- Transformation -- Epigenetics; Biochemistry -- Periodicals; Cytology -- Periodicals; Biochemistry -- Periodicals; Cell Biology -- Periodicals; Biochimie -- Périodiques; Cytologie -- Périodiques; Biochimie; Cytologie; Biochemistry; Cytology; Ressource Internet (Descripteur de forme); Périodique électronique (Descripteur de forme); Periodicals; 572.05
• DOI: 10.1016/j.biocel.2022.106263
• Languages: English
• ISSNs: 1357-2725

Abstract

Abstract: Cancers are genetically divergent but intriguingly display similar patterns of epigenetic deregulation, including global DNA hypomethylation and hypermethylation of promoter CpG islands. Early developmental programmes mirror this cancer epigenome suggesting that reactivation of embryonic programmes is essential to the initiation of cancer. We propose a scenario where two waves of dedifferentiation underlie key cell transitions: the first from normal to cancer, and the second driving malignancy. The possibility that early developmental programmes underpin both normal development and the switch to cancer has huge therapeutic implications. The reignition of embryonic programmes and pluripotency networks in seemingly healthy tissues could provide unique cellular targets, to eliminate pre-cancerous or cancer promoting cells before they have the opportunity to form tumours. We conclude that focusing on epigenetic gatekeepers, and peri-implantation cellular identities, could transform the diagnosis and prevention of cancer, especially if these programmes crosscut many cancer types, solid and haematological. Highlights: The somatic mutation theory is insufficient to explain the pathogenesis of many cancers. Mammalian cells are reprogrammed in response to physiological stresses. Reactivation of early embryonic programmes is associated with tumorigenesis. Cellular transformation may be related to an immature epigenetic landscape. Dedifferentiation is a driver of cancer progression regardless of genetic context.