Circadian Clock's Cancer Connections

The circadian molecular clock regulates and coordinates cellular metabolism with the organism's daily feeding and fasting cycle. Disruption of circadian rhythm, such as through jet lag or shift work, appears to heighten cancer risk in humans and accelerates tumorigenesis in animal models. The mammalian clock is a circuitry of transcription factors anchored by BMAL1-CLOCK, which drives diurnal oscillation of metabolic gene expression. The clock is independent of the cell cycle, but they can couple to coordinate normal cell proliferation. Expression of components of the clock, BMAL1 and PER2, appears decreased in human cancers. PER2 promotes p53 function, while BMAL1 expression is suppressed by MYC, linking key oncogenic drivers to the circadian clock. This review provides an overview of the clock, its regulation of metabolism, the connection to cancer shown in studies spanning from human epidemiology to cell biology, and the therapeutic implications of the circadian rhythm.