Disrupted Circadian Rhythms Enhance Lung Tumor Growth in Mice

Scientists discovered an important molecular link between lung tumor growth and disrupted circadian rhythms, according to a new paper co-authored by a University of Rochester 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. The World Health Organization has proclaimed that disrupted circadian rhythms are a probable carcinogen.

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.

Reference: Pariollaud M, Ibrahim LH, Irizarry E, et al. Circadian disruption enhances HSF1 signaling and tumorigenesis in Kras-driven lung cancer. Sci Adv. 2022;8(39):eabo1123. doi: 10.1126/sciadv.abo1123

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