What Happens if Your Circadian Rhythms are Out of Whack?

Sep. 28, 2023

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Cancer cells that carry a certain gene will grow rapidly and divide after shutting down their own circadian rhythms, a new Wilmot Cancer Institute study shows.

The scientific team led by Brian Altman, PhD, investigates how circadian rhythms—sometimes known as the “biological clock”—can lead to cancer when disrupted. In people, a disruption of the biological clock can be caused by uneven sleep, jet lag, night shift work, or even nighttime snacking.

In this latest study, the team looked at what happens deep inside cancer cells, each of which has its own 24-hour cycle.

Researchers discovered that the MYC oncogene shuts down circadian rhythms in cancer cells, stopping circadian rhythms in up to 85 percent of the genes in cancer cells, and changing the time of day in which cell metabolism peaks. The team hypothesizes that this gives cancer cells an advantage and can quicken tumor initiation by releasing the cell’s normal processes from circadian control.

The MYC gene is very common, being implicated in about one-third of all cancers, including lung, liver, breast, blood, colon, pancreas, and skin.

Juliana Cazarin de Menezes, PhD, a postdoctoral fellow in the Altman Lab, and technician Rachel DeRollo, are co-first authors of the new study, which was published in PLoS Genetics.

Original article was published on October 21, 2022.

Scientists discovered an important molecular link between lung tumor growth and disrupted circadian rhythms, according to a new paper co-authored by a Wilmot Cancer Institute investigator and led by the Scripps Research Institute in California.

Circadian rhythms, sometimes called the “biological clock,” is the cellular process that rules sleep-wake cycles. Jet lag, nighttime snacking, lack of sleep, or irregular work schedules can wreck circadian rhythms. The World Health Organization has proclaimed that disrupted circadian rhythms are a probable carcinogen.

head shot of Brian Altman, PhD
Brian Altman, Ph.D.

The latest research, published in the high-impact journal Science Advances, describes that when the circadian clock gets off track it implicates a cancer-signature gene known as HSF1 that can trigger lung tumors. Lungs are under tight circadian control and seem to be particularly vulnerable to a disrupted biological clock.

The paper describes in mouse models the role of HSF1 signaling, a previously unknown mechanism that may explain tumor formation in response to rhythm disruption.

The findings also suggest that it may be possible to target HSF1 with drug therapy, to prevent cancer among people with frequently disturbed circadian rhythms.

Although this study was done in mice, other data link circadian disruption to human tumors, said co-author Brian Altman, Ph.D., an assistant professor of Biomedical Genetics at the University of Rochester Medical Center and a Wilmot faculty member.

“Everything points in the same direction,” he said. He noted that in this case, when the circadian clocks in mice are disrupted by inconsistent sleep, for example, the outcomes are highly relevant to people who work night shifts or rotating schedules.

Altman’s chief contribution to the study was to provide expertise on a scientific method to assess how the circadian clock behaves in tissues. The Scripps team reached out to Altman to collaborate after seeing a presentation he gave at a scientific meeting on use of the technique, which was invented in 2018 at Vanderbilt University by Jacob Hughey, Ph.D. Altman and his lab have been focused on circadian rhythms and the connection to cancer for several years.

Lead author of the study is Katja Lamia, Ph.D., associate professor of Molecular Medicine at Scripps. Funding was provided by the National Science Foundation and the National Institutes of Health.