Changes in temperature may be behind the link between circadian disruption and cancer

Disruptions in the circadian rhythm, the ways in which our bodies change in response to the 24-hour cycle of light and dark, have been linked to many different diseases, including cancer. The relationship between the two is not well understood, although shift workers and others with irregular schedules regularly experience these disorders. But a new finding from Scripps research helps answer what might be behind this link.

Posted in science progress On September 28, 2022, results highlighted that chronic daily disruption significantly increased lung cancer growth in animal models. By identifying the genes involved, researchers are highlighting the mysterious link between our sleep patterns and disease, which could help inform everything from developing more targeted cancer treatments to better monitoring at-risk groups.

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“There has always been a lot of evidence that shift workers and others with interrupted sleep schedules have higher rates of cancer, and our task in this study was to find out,” says lead researcher Katia Lamia, PhD, assistant professor in the department. the reason”. Molecular medicine.

To answer this question, the scientists used a mouse model with expressed KRAS – the most common gene in lung cancer. Half of the mice were housed in a ‘normal’ light cycle, that is, 12 h of light and 12 h of dark. The other half was housed in a light cycle supposedly similar to that of shift workers, with light hours moved eight hours earlier every two or three days.

The results are consistent with what the researchers initially thought: The mice exposed to the changing, irregular patterns of light had a 68% increased tumor burden.

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But when they used RNA sequencing to identify the different genes involved in cancer growth, they were surprised that the group in the family of heat shock factor 1 (HSF1) proteins was the main culprit.

“This is not the mechanism we expected to find here. HSF1 has been shown to increase rates of tumor formation in several different models of cancer, but it has never been linked to circadian disruption before,” says Lamia.

The HSF1 genes are responsible for making sure proteins are still made properly even when the cell is under extreme stress — in this case, when it is exposed to changes in temperature. The team suspects that HSF1 activity increases in response to circadian disruption because changes in our sleep cycles disturb the circadian rhythms of our body temperature.

“Normally, our body temperature changes by a degree or two while we sleep. If shift workers don’t experience this natural drop, it could interfere with how the HSF1 pathway normally functions–and eventually lead to more dysregulation in the body,” she adds. She believes that Cancer cells may exploit the HSF1 pathway for their own benefit and create mutated and denatured proteins, but she says more research is needed in this area.

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These findings not only help shape our understanding of how circadian rhythms affect cancer, but also a potential preventative method for protecting the most vulnerable and at-risk groups. With non-invasive monitoring of body temperature, it may be possible to improve shift workers’ schedules and even stop the kind of dysregulation that can lead to cancer.

With these discoveries in hand, scientists are now assessing whether HSF1 signaling is required for increased tumor burden rather than just an association.

“Now that we know there is a molecular link between HSF1, circadian disruption and tumor growth, our task is to determine how they are all related,” Lamia says.


Scripps Research Institute

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