Disruptions in circadian rhythm have been linked to many different diseases, including cancer. However, the connection between the two has not been fully understood. Now, a new mouse study by scientists at Scripps Research uncovers what may be behind this correlation.

Their findings are published in the journal Science Advances in an article titled, “Circadian disruption enhances HSF1 signaling and tumorigenesis in Kras-driven lung cancer.”

“Disrupted circadian rhythmicity is a prominent feature of modern society and has been designated as a probable carcinogen by the World Health Organization,” wrote the researchers. “However, the biological mechanisms that connect circadian disruption and cancer risk remain largely undefined. We demonstrate that exposure to chronic circadian disruption [chronic jetlag (CJL)] increases tumor burden in a mouse model of KRAS-driven lung cancer.”

“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,” said senior author Katja Lamia, PhD, associate professor in the department of molecular medicine.

The scientists used a mouse model with expressed KRAS. Half of the mice were housed in a “normal” light cycle (12 hours of light and 12 hours of darkness.) The other half were housed in a light cycle meant to resemble that of shift workers, where the light hours were moved earlier by eight hours every two or three days.

The scientists observed mice that were exposed to the irregular, shifting light patterns had an increased tumor burden of 68%.

The scientists observed further using RNA sequencing to determine the different genes involved in cancer growth. The scientists were surprised to find that a collection in the heat shock factor 1 (HSF1) family of proteins was the culprit.

“This is not the mechanism we were expecting 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,” Lamia explained.

“Normally, our body temperature changes by one or two degrees while we’re sleeping. If shift workers don’t experience that normal drop, it could interfere with how the HSF1 pathway normally operates—and ultimately lead to more dysregulation in the body,” Lamia added.

Their findings suggest cancer cells may exploit the HSF1 pathway to their own benefit and create mutant, misfolded proteins, but further research is needed to confirm this.

The scientists are now diving deeper to determine whether HSF1 signaling is required to increase tumor burden and isn’t solely just a correlation.

“Now that we know there’s a molecular link between HSF1, circadian disruption, and tumor growth, it’s our job to determine how they’re all connected,” Lamia concluded.

The research illuminates the link between our sleeping patterns and disease, which could lead to the development of more targeted cancer treatments.

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