WhatsNew2Day
Latest News And Breaking Headlines

New research reveals circadian clock influences cell growth, metabolism and tumor progression

a) Schematic of the initiation and progression of CRC via Apc, Bmal1 and additional mutations . (B) In vivo gut-specific gene targeting strategy for Bmal1 and Apc. (C) Linearized ileal tissue from representative mice of all genotypes. (d) Overview of Representative Sections of Hematoxylin and Eosin (H&E) Stained Swiss Rolls in the Small Intestine of WT, Bmal1/− , Apc+/− and Apc+/−;Bmal1/− mice. Scale bars, 1 mm. (E) Scatterplot of the number of polyps in the small intestine from 30 WT, 30 Bmal1/−29 Apc+/− and 62 Apc+/−;Bmal1/− mice . (f) Scatterplot of individual polyp sizes from the small intestine of Apc+/− and Apc +/−;Bmal1/− mice (n = 8 mice per genotype). (G) Kaplan-Meier survival curve of 9 to 11 mice by genotype up to 18 months. (huh) Scatterplot of the number of polyps in the small intestine from six Apc+/− mice kept in 12 hours of light:12 hours (12:12) dark conditions and six Apc+/−mice kept in shift work interruptions (SD). (I) Scatterplot of individual small bowel polyp sizes from 12:12 and SD Apc+/− mice. Data represent the mean ± SEM, and statistical significance was determined by one-way analysis of variance (ANOVA) using Tukey’s multiple comparison test for (E), log-rank (Mantel-Cox) test for (G), and Student’s unpaired t test for (F), (H) and (I). Asterisks represent p-values ​​of t test or multiple comparisons, with *p < 0.05 and ****p < 0.0001. Credit: Science Progress (2022). DOI: 10.1126/sciaadv.abo2389″ width=”800″ height=”530″/>

Disruption of the circadian clock accelerates intestinal tumorigenesis in vivo.(A) Schematic representation of the initiation and progression of CRC by Apc, Bmal1and additional mutations. (B) In vivo gut-specific gene targeting strategy for: Bmal1 and Apc. (C) Linearized ileal tissue from representative mice of all genotypes. (d) Overview of Representative Sections of Hematoxylin and Eosin (H&E)-stained Small Intestine Swiss Rolls from WT, Bmal1/−, Apc+/−and Apc+/−;Bmal1/− mice. Scale bars, 1 mm. (E) Scatterplot of the number of polyps in the small intestine from 30 WT, 30 Bmal1/−29 Apc+/−and 62 Apc+/−;Bmal1/− mice. (f) Scatterplot of individual polyp sizes from the small intestine of Apc+/− and Apc+/−;Bmal1/− mice (n = 8 mice per genotype). (G) Kaplan-Meier survival curve of 9 to 11 mice by genotype up to 18 months. (huh) Scatter plot of the number of polyps in the small intestine from six Apc+/− mice kept in 12 hours of light: 12 hours (12:12) dark conditions and six Apc+/− mice maintained in shift disruption (SD) conditions. (l) Scatterplot of individual polyp sizes from the small intestine from 12:12 and SD Apc+/− mice. Data represent the mean ± SEM, and statistical significance was determined by one-way analysis of variance (ANOVA) using Tukey’s multiple comparison test for (E), log-rank (Mantel-Cox) test for (G), and Student’s unpaired t test for (F), (H) and (I). Asterisks represent p values ​​of t test or multiple comparisons, with *p < 0.05 and ****p < 0.0001. Credit: Scientific progress (2022). DOI: 10.1126/sciaadv.abo2389

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.


Loss of circadian regulation increases glucose production during lung cancer


More information:
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

Provided by the University of California, Irvine

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

This document is copyrighted. Other than fair dealing for personal study or research, nothing may be reproduced without written permission. The content is provided for informational purposes only.

This website uses cookies to improve your experience. We'll assume you're ok with this, but you can opt-out if you wish. Accept Read More