Scientists discovered that disrupted circadian rhythms activate the gene HSF1, leading to lung tumor formation.
An important molecular link between lung tumor growth and disrupted circadian rhythms has been uncovered by scientists. The discovery is presented in 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,” are the cellular processes that rule sleep-wake cycles. Jet lag, nighttime snacking, lack of sleep, or irregular work schedules can mess up circadian rhythms. According to the World Health Organization (WHO), disrupted circadian rhythms are a probable carcinogen as a result of both population and laboratory-based findings.
Published in the high-impact journal Science Advances, the latest study 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 research paper describes the role of HSF1 signaling in mouse models. This previously unknown mechanism may explain tumor formation in response to rhythm disruption.
Potential for Drug Therapy Targeting HSF1
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: “Circadian disruption enhances HSF1 signaling and tumorigenesis in Kras-driven lung cancer” by Marie Pariollaud, Lara H. Ibrahim, Emanuel Irizarry, Rebecca M. Mello, Alanna B. Chan, Brian J. Altman, Reuben J. Shaw, Michael J. Bollong, R. Luke Wiseman and Katja A. Lamia, 28 September 2022, Science Advances.
DOI: 10.1126/sciadv.abo1123
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.
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