All organisms have a circadian rhythm. In plants, for example, circadian rhythm helps sense light, temperature, length of the day, and season change to fine-tune processes such as photosynthesis, growth, flowering mechanisms, etc. In humans, the circadian rhythm refers to the body’s physiological response to light and dark changes in 24 hours. The human sleep cycle is the most visible example of the circadian rhythm. However, circadian rhythm affects much more than sleep; it can regulate bodily function at the cellular level and even determine which genes are turned off or on.
Chronic disruption of the circadian rhythm has been previously correlated with increased cancer risk. However, the underlying connection between the two has remained poorly understood. A recent study published in Science Advances has unraveled the mechanism by which the disruption of the circadian rhythm can influence susceptibility to cancer. The study was initiated to understand why disrupted sleep results in higher cancer rates. Scientists used a mouse lung cancer model in which a human gene (KRAS) commonly mutated in human lung cancer was intentionally expressed. Two groups of KRAS-dependent lung cancer mice were exposed to either normal or abnormal light cycles. The abnormal light cycle was the experimental condition that induced a disrupted circadian rhythm. The experimental mice demonstrated a significant increase in tumor growth compared to the control group, confirming that pathways of the circadian cycle may directly influence cancer growth.
The investigators looked a little further into this connection. They wanted to understand what exactly the circadian disruption was triggering that caused an increase in tumor growth. Using RNA sequencing to study gene expression, they identified a specific family of genes (called HSF 1) that were expressed in response to the disruption in mice. The HSF 1 (heat shock factor 1) is normally expressed in response to stress. In this case, the cancer cells could thrive better with a disordered HSF 1 pathway. Thus, the circadian rhythm disruption increased cancer risk via the dysregulation of the HSF 1 pathway. Understanding this specific molecular link between cancer and circadian rhythm can be powerful. It can be used to design not only interventions for cancer patients in the future but also preventions for at-risk individuals. Katja Lamia, associate professor at Scripps Research Institute and the senior author of this study, says, "There has always been a lot of evidence that shift workers and others with disrupted sleep schedules have higher rates of cancer, and our mission for this study was to figure out why,"
Sources: Science Daily, Science Advances, Hopkins Medicine
