The role of circadian regulation in cancer.
Proper circadian regulation is essential for the well being of the organism, and disruption of circadian rhythms is associated with pathological conditions including cancer. In mammals, the core clock genes, Per1 and Per2, are key regulators of circadian rhythms both in the central clock in the hypothalamous and in peripheral tissues. Recent findings revealed molecular links between Per genes and cellular components that control fundamental cellular processes such as cell division and DNA damage. New data also shed light on mechanisms by which circadian oscillators operate in peripheral organs to influence tissue-dependent metabolic and hormonal pathways. Circadian cycles are linked to basic cellular functions, as well as to tissue-specific processes through the control of gene expression and protein interactions. By controlling global networks such as chromatin remolding and protein families, which themselves regulate a broad range of cellular functions, circadian regulation impinges upon almost all major physiological pathways. These molecular insights illustrate how disregulation of circadian rhythms might influence the susceptibility to cancer development and provide further support for the emerging role of circadian genes in tumor suppression.
Gery
S
S
Unniversity of California School of Medicine, Los Angeles, California 90048, USA.
Koeffler
H P
HP
D000818:Animals; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology; D002843:Chromatin / Q000235:genetics; D002940:Circadian Rhythm / Q000235:genetics / Q000502:physiology*; D004249:DNA Damage; D005260:Female; D006728:Hormones / Q000502:physiology; D006801:Humans; D008297:Male; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology; D056950:Period Circadian Proteins; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
D018797:Cell Cycle Proteins; D002843:Chromatin; D006728:Hormones; D009687:Nuclear Proteins; C539022:PER1 protein, human; C421902:PER2 protein, human; D056950:Period Circadian Proteins; D014157:Transcription Factors