New research reveals circadian clock influences cell growth, metabolism and tumor progression
In a new Irvine-led study from the University of California, researchers define how the circadian clock affects cell growth, metabolism and tumor progression. Their research also reveals how disruption of the circadian clock affects genome stability and mutations that may further drive critical tumor-promoting pathways in the gut.
The study, titled, “Disruption of the Circadian Clock Drives Apc Loss of Heterozygous to Accelerate Colorectal Cancer,” was published today in Scientific progress.
In this study, researchers found that both genetic and environmental disruption of the circadian clock contribute to the mutation of the adenomatous polyposis coli (APC) tumor suppressor, which is found in the vast majority of human colorectal cancers (CRC). APC point mutations, deletions, and loss of heterozygosity (LOH) events have been reported in approximately 80 percent of human CRC cases, and it is these mutations that drive the initiation of intestinal adenoma development.
“As a society, we are exposed to several environmental factors that affect our biological clock, including night shifts, prolonged light exposure, changes in sleep/wake cycles, and altered feeding behavior,” said Selma Masri, Ph.D., assistant professor of biological chemistry at the University of Groningen. UCI School of Medicine. Strikingly, we have seen an alarming increase in several young-onset cancers, including colorectal cancer. The underlying cause of this increased incidence of cancer in adults between the ages of 20 and 30 remains undefined. Based on our findings, we believe Now, however, that disruption of the circadian clock plays an important role.”
According to the National Institutes of Health, there is an alarming increase in early colorectal cancer in young individuals. Today, nearly 10 percent of CRC cases are now diagnosed in people under the age of 50, and this trend is steadily increasing. Suspected risk factors include environmental aspects, such as lifestyle and dietary factors, which are known to influence the circadian clock.
APC mutations are also associated with second hits in major oncogenic pathways, including Kras, Braf, p53 and Smad4, and these mutations drive progression to adenocarcinoma, collectively contributing to disease progression. These findings now imply a disruption of the circadian clock in driving additional genomic mutations critical for accelerating colorectal cancer.
The circadian clock is an internal biological pacemaker that regulates many physiological processes. Research in the Masri Lab is mainly focused on how disruption of the circadian clock is involved in the development and progression of certain cancers. Researchers in the Masri Lab are actively conducting further research to determine how the circadian clock affects other cancer types.
Sung Kook Chun et al, Disruption of the circadian clock causes Apc loss of heterozygosity to accelerate colorectal cancer, Scientific progress (2022). DOI: 10.1126/sciaadv.abo2389
Quote: New Research Reveals Circadian Clock Affects Cell Growth, Metabolism, and Tumor Progression (2022, Aug. 10) retrieved Aug. 10, 2022 from https://phys.org/news/2022-08-reveals-circadian-clock-cell-growth. html
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