The Science sub-journal emphasizes the importance of temperature: a surprising link between circadian rhythm disorders and cancer

The disruption of circadian rhythms — the way our bodies change their 24-hour circadian cycle — has been linked to many different diseases, including cancer
.
Although shift workers and other people with irregular schedules often experience these disturbances, little
is known about the connection between the two.
But a new finding from Scripps Research helps answer the reasons
behind this correlation.

This finding highlights that chronic circadian rhythm disorders significantly increase the growth
of lung cancer in animal models.
By identifying relevant genes, researchers have revealed mysterious links between our sleep patterns and disease, which may help develop more targeted cancer treatments, as well as better monitor at-risk populations
.

Dr Katja Lamia, associate professor and senior author in the Department of Molecular Medicine, said: "There has always been a lot of evidence that shift workers and other people whose sleep hours are disrupted are more likely to develop cancer, and our task in this study was to find out why
.
"

To answer this question, the scientists used a mouse model expressing KRAS — the most common mutated gene
in lung cancer.
Half of the mice were placed in a "normal" light cycle, i.
e.
12 h of light and 12 h of darkness
.
The other half were placed in a lighting cycle similar to that of shift workers, with their lighting hours advanced by 8 hours every two or three days
.

The findings were consistent with the researchers' initial thinking: Mice exposed to irregular, ever-changing patterns of light increased tumor burden by 68 percent
.

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

"It's not the mechanism
we expect to find here.
In several different cancer models, HSF1 has been shown to increase the rate of tumor formation, but it has never been found to be associated with circadian rhythm disorders before," Lamia said
.

The HSF1 gene is responsible for ensuring that proteins are synthesized
correctly even when cells are under extreme pressure (in this case, when cells undergo temperature changes).
The team suspects that the increase in HSF1 activity is a response to circadian disruptions because changes in our sleep cycle disrupt the daily rhythm
of our body temperature.

"Usually, our body temperature changes one or two degrees
when we sleep.
If shift workers do not experience a normal decline, it could interfere with the proper functioning of the HSF1 pathway and ultimately lead to more physical disorders," Lamia added
.
Cancer cells may use the HSF1 pathway for their own benefit and produce mutated, misfolded proteins, she said, but more research
is needed in this area.

These findings may not only help us understand the effects of circadian rhythms on cancer, but may also help us find a preventative way to protect vulnerable people
at risk.
With noninvasive monitoring of body temperature, it is possible to optimize shift workers' schedules and even stop this disorder
that can lead to cancer.

With these findings, scientists are now evaluating whether HSF1 signaling needs to increase tumor burden, not just a correlation
.

"Now that we know that there is a molecular link between HSF1, circadian rhythm disorders, and tumor growth, our job is to identify the link between them," Lamia said
.

Circadian disruption enhances HSF1 signaling and tumorigenesis in Kras-driven lung cancer