Scientists discover molecular connection between lung tumor growth and disrupted circadian rhythms

Scientists discover molecular connection between lung tumor growth and disrupted circadian rhythms

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

The circadian rhythm, sometimes called the “biological clock,” is the cellular process that controls the sleep-wake cycle. The World Health Organization has stated that disrupted circadian rhythms are likely carcinogenic.

The latest study, published in the prestigious journal Science Advances, describes that when the circadian clock goes out of sync, a cancer signature gene called HSF1 can trigger lung tumors. The lungs are under strict circadian control and appear to be particularly vulnerable to a disrupted biological clock.

The article describes the role of HSF1 signaling in mouse models, a previously unknown mechanism that could explain tumorigenesis in response to arrhythmias.

The results also suggest that it may be possible to target HSF1 with drug therapy to prevent cancer in people with commonly disrupted circadian rhythms.

Although this study was conducted in mice, other data link circadian disruptions to human tumors, said co-author Brian Altman, Ph.D., 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, if circadian clocks in mice are disrupted by, for example, irregular sleep, the results are very important for people who work night shifts or alternating work schedules.

Altman's main contribution to the study was to provide expertise on a scientific method for assessing circadian clock behavior in tissues. The Scripps team approached Altman to work with him after seeing a presentation he gave at a scientific meeting about the use of the technique, which was invented in 2018 at Vanderbilt University by Jacob Hughey, Ph.D. Altman and his lab have been focusing 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. The Scripps press release is here. Funding was provided by the National Science Foundation and the National Institutes of Health.

Source:

University of Rochester Medical Center

Reference:

Pariollaud, M., et al. (2022) Circadian disruption enhances HSF1 signaling and tumorigenesis in Kras-related lung cancer. Scientific advances. doi.org/10.1126/sciadv.abo1123.

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