Study defines how the circadian clock influences cell growth, metabolism and tumor progression

Study defines how the circadian clock influences cell growth, metabolism and tumor progression

In a new study led by the University of California, Irvine, researchers define how the circadian clock influences cell growth, metabolism and tumor progression. Her research also shows how disrupting the circadian clock impacts genome stability and mutations that can further drive critical tumor-promoting pathways in the gut.

The study, titled “Circadian Clock Disruption Drives APC Loss of Heterozygosity to Accelerate Colorectal Cancer.” was published today in Science Advances.

In this study, researchers found that both genetic and environmental disruptions of the circadian clock contribute to the mutation of the adenomatous polyposis coli (APC) tumor suppressor, which is present 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 influence our biological clock, including night shift work, prolonged exposure to light, changes in the sleep-wake cycle, and changes in eating habits. Notably, we have observed an alarming increase in several young cancers, including colorectal cancer. The underlying cause of this increased cancer incidence in adults in their 20s and 30s remains undefined. However, based on our findings, we now believe that disrupting the circadian clock plays an important role.”

Selma Masri, PhD, assistant professor of biological chemistry at the UCI School of Medicine

According to the National Institutes of Health, there has been an alarming increase in early-stage colon cancer among young people. Today, nearly 10 percent of CRC cases are 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 key oncogenic pathways, including Kras, Braf, p53, and Smad4, and these mutations drive progression to adenocarcinoma and collectively contribute to disease progression. Our results now suggest that circadian clock disruption drives additional genomic mutations critical to accelerating colorectal cancer.

The circadian clock is an internal biological pacemaker that regulates numerous physiological processes. Research in the Masri Lab primarily focuses on how disruption of the circadian clock is involved in the development and progression of certain types of cancer. Researchers at Masri Lab are actively pursuing further research aimed at defining how the circadian clock affects other types of cancer.

Source:

University of California – Irvine

Reference:

Chun, SK, et al. (2022) Circadian clock disruption drives Apc loss of heterozygosity to accelerate colorectal cancer. Scientific advances. doi.org/10.1126/sciadv.abo2389.

.