Disturbed circadian rhythm is a typical feature of modern society. In addition to people who work night shifts, many people also like to stay up late, and their work and rest are very irregular. While staying up late can be great, the consequences are severe: Circadian rhythm disruption has been identified as a risk factor for diseases such as obesity, cardiovascular disease and cancer. Working night shifts is even listed as one of the probable carcinogens by the World Health Organization.
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How does circadian rhythm disruption increase cancer risk? Scientists have been exploring the specific mechanism, and today I will introduce the latest research to you.
Irregular biological clock, lung cancer grows faster
Findings1, published September 28, 2022 in the journal Science Advances, show that chronic circadian disruption significantly increases lung cancer growth in mice, possibly through Heat shock protein-mediated, heat shock proteins have been shown to increase tumor formation in several different cancer models.
The researchers studied a mouse model with a mutation in the KRAS gene. KRAS is a commonly mutated gene in lung cancer and often drives the development of lung cancer due to mutations.
Half of the mice were housed on a normal, regular light cycle of 12 hours of light and 12 hours of darkness. The other half of the mice were placed on an irregular light cycle similar to shift work, where the light time was advanced by 8 hours every two or three days.
It was found that after 20 weeks, tumor burden increased by 68% in mice exposed to irregular light patterns, That is to say, long-term biological clock disorders, lung cancer grows faster.
Figure 1. Mice exposed to irregular light patterns (CJL) had a 68% increase in tumor burden compared to mice exposed to regular light (12:12LD).
What role do heat shock proteins do?
The researchers found that when mice were exposed to irregular light patterns, a class of genes was significantly up-regulated: heat shock proteins.
Heat shock proteins, as their name implies, are expressed at higher temperatures. When cells are in a relatively high temperature environment, various biological processes in the cells may be affected by the high temperature and function abnormally. To keep functioning properly, cells make heat shock proteins to assist in various biological processes, such as allowing proteins to fold properly. That is, heat shock proteins are a stress response of cells.
Stress response can help cells or organisms cope with crises when they occasionally encounter danger, but if the cells or organisms are under stress for a long time, there is a problem. Normally, our body temperature is one or two degrees lower when we sleep than when we are active during the day, and when the circadian rhythm is disturbed, such as not sleeping when it is time to sleep, the body continues to be in a state of higher temperature, and Promotes the expression of heat shock proteins. This abnormal expression interferes with the normal operation of the heat shock protein pathway and keeps cells in a state of continuous stress, which may eventually lead to more dysregulation and abnormalities and promote the occurrence of cancer.
In fact, in many cancers, the expression of heat shock proteins is greatly increased. A lot of evidence shows that heat shock proteins are involved in many key mechanisms of malignant transformation and progression of tumors, including stimulating proliferation, evading apoptosis, promoting angiogenesis, invasion and metastasis to surrounding tissues, etc. Because of this, heat shock proteins have long been targeted by researchers, hoping to inhibit tumor growth by inhibiting heat shock proteins.
How to deal with the risk of circadian rhythm disturbance?
To deal with the risk of circadian rhythm disturbance, the most direct and most effective way is to maintain a normal and regular work and rest. Especially in people who already have cancer, circadian rhythm disturbances are likely to contribute to the development of cancer, so maintaining a regular schedule is especially important.
For people who must frequently work night and shift shifts, consider temperature monitoring to optimize shift schedules. In addition, although the development of anti-heat shock protein anticancer drugs has not been smooth and has not shown efficacy in unselected patients, it is possible that such drugs have a potential inhibitory effect on cancer occurrence in people who need to work night and shift shifts . In the future, there will be studies of this type, and the cancer degree will be interpreted for everyone at the first time!
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1. Pariollaud, M. et al. Circadian disruption enhances HSF1 signaling and tumorigenesis in Kras-driven lung cancer. Sci. Adv. 8, eabo1123 (2022).