How your circadian clock influences cell metabolism and tumour progression

How your circadian clock influences cell metabolism and tumour progression

Disruption of your circadian clock by poor sleep, environment, dietary and lifestyle factors can influence your metabolism, cell growth and increase cancer risk and progression in colorectal cancer. This is likely to be true for many other cancers.

In a new study (1) by University of California, Irvine, researchers looked at the links between disruption in the Circadian rhythms and colorectal cancer, finding that both genetic disruption and environmental disruption of the circadian clock accelerate Apc-driven CRC pathogenesis, in vivo. In particular, the researchers were concerned about the rapid rise in cases of CRC in adults younger than 60 years of age.

According to Johns Hopkins Medicine (2), Adenomatous Polyposis Coli (APC) is a gene that suppresses tumour growth. If the APC gene becomes defective and unstable it becomes more susceptible to further changes that may lead to colon and rectal cancers. Instability in APC sets of a chain reaction influencing β-catenin, T cell factor/lymphoid enhancer factor, and ultimately Wnt-dependent gene expression.

In addition, APC mutations are associated with second effects in key adenocarcinoma cancer pathways, including Braf, Kras, p53, and Smad4. CRC tumours have been shown to posses disrupted ‘human circadian clock genes’ when compared to healthy colon epithelial cells.

Moreover, this is not atypical and human data from The Cancer Genome Atlas (TCGA) shows a significant correlation between disruption in certain core clock genes and cancer pathways, survival rates, and tumour aggression in 32 different cancer types (3).

The researchers in the Irvine study used light shift techniques which showed that disruption of the circadian clock accelerated tumour burden and accelerated a loss of homeostasis in Bmal then Apc. This, in turn, activated Wnt signalling driving cancer signalling and progression.

In mice with circadian disruption more Bmal and Apc disruption was found along with more polyps, in both male and females.

Organoids of human tissue, and live mice were used in the experiments.

Go to: Melatonin and health - essential in cancer prevention, inflammatory diseases and anti-aging

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References

  1. Disruption of the circadian clock drives Apc loss of heterozygosity to accelerate colorectal cancer - Sung Kook Chun et al;  Sciences Advances, 10 August 2022; VOL. 8, NO. 32 - https://www.science.org/doi/10.1126/sciadv.abo2389 

  2. Johns Hopkins - APC and Colorectal cancer - https://www.hopkinsmedicine.org/health/conditions-and-diseases/colon-cancer/apc-i1307k-and-colorectal-cancer

  3. The genomic landscape and pharmacogenomic interactions of clock genes in cancer chronotherapy.  Y. Ye, Y. Xiang, F. M. Ozguc, et al; Cell Syst. 6, 314–328.e2 (2018).

2022 Research
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