Disruptions to Your Body's Circadian Cycle and Potential Consequences
The latest research, published in the high-impact journal Science Advances, has shed light on a critical mechanism that may explain tumor formation in response to rhythm disruption. The study, conducted by Katja Lamia, Ph.D., associate professor of Molecular Medicine at Scripps, presents the role of HSF1 signaling in this process.
According to the study, the MYC oncogene is implicated in about one-third of all cancers, including lung, liver, breast, blood, colon, pancreas, and skin. This oncogene was found to shut down circadian rhythms in cancer cells, affecting up to 85 percent of the genes in cancer cells and changing the time of day in which cell metabolism peaks.
Lungs are particularly vulnerable to a disrupted biological clock, the study suggests. To investigate this further, the Scripps team reached out to Brian Altman, Ph.D., an assistant professor of Biomedical Genetics at the University of Rochester Medical Center and a Wilmot faculty member, who contributed expertise on a scientific method to assess how the circadian clock behaves in tissues for the study.
The collaboration between the two teams revealed that MYC as a transcription factor enhances the expression of REV-ERB (a nuclear receptor and circadian repressor), which inhibits BMAL1, a core positive transcriptional activator in the circadian clock feedback loop. This disruption disables the circadian control of cellular functions, including metabolism. MYC also directly upregulates glucose transporter 1 (GLUT1) and most glycolytic enzymes, shifting cancer cells towards enhanced glucose uptake and glycolysis—a hallmark of cancer metabolism known as the Warburg effect.
The study also found an important molecular link between lung tumor growth and disrupted circadian rhythms. The findings suggest that targeting HSF1 with drug therapy could be a potential therapeutic strategy to counteract MYC-driven cancer cell proliferation.
It's worth noting that uneven sleep, jet lag, night shift work, or nighttime snacking can cause a disruption of the biological clock in people. The study's implications could have significant implications for understanding the link between disrupted circadian rhythms and cancer.
The research was funded by the National Science Foundation and the National Institutes of Health. The study was co-authored by Juliana Cazarin de Menezes, Ph.D., and technician Rachel DeRollo, who are listed as co-first authors. The original article was published on October 21, 2022, in PLoS Genetics.
In summary, the study reveals a critical mechanism by which oncogenes reprogram cellular physiology to favour cancer. By understanding this connection, researchers may be able to develop new strategies to counteract MYC-driven cancer cell proliferation and potentially reduce the risk of cancer among individuals with frequently disturbed circadian rhythms.
