August 3, 2016
Our body is designed to sleep at night and work during the day. A new study by Massachusetts Institute of Technology (MIT) biologists shows that working night shifts or disrupting the body’s internal clock may lead to cancer growth.
Until now, nobody had a clue why disrupting the biological clock, which drives circadian rhythms, has such an impact on human health. MIT scientists believe they can offer an explanation. They think they have figured out the mystery of the heightened cancer risk.
Circadian rhythms function as tumor suppressors
Circadian rhythms are found in most living organisms. They follow a 24-hour cycle, and influence sleep-wake cycles, mood, alertness, hormone release, body temperature and other vital functions. Abnormal circadian rhythms have been associated with sleeping disorders, obesity, diabetes, depression, bipolar disorder and seasonal affective disorder. And now cancer can be added to the list.
In mice, the team found that two genes, Bmal1 and Per2, known to control the circadian rhythms of a cell, also suppress tumor growth. According to Thales Papagiannakopoulos, a former postdoc at MIT’s Koch Institute for Integrative Cancer Research and the lead author of the study, disruption of these genes, either through gene deletion or disruption of the normal light/dark cycle, allows tumors to become more aggressive.
How working night shifts may increase cancer risk
Our body and brain are hardwired to relax and unwind after dark and spring back into action in the morning. The circadian clock is located in the brain’s suprachiasmatic nucleus (SCN). The SCN can be seen as a local communication center; it receives information about light levels from the retina and passes this information on to the cells.
The information the cell receives will either activate or deactivate a set of genes (including Bmal1 and Per2) known to control circadian activities. Furthermore, Bmal1 and Per2 regulate a cancer-promoting protein known as the c-myc. When their function is interrupted, c-myc is given free rein to accumulate and spin out of control.
“Cells need the light cue, which is like a reset button for the clock. When you lose that cue, you lose the normal rhythms in every cell in your body,” said Papagiannakopoulos.
For the study, they exposed mice, predisposed to develop a particular type of lung cancer, to either a regular day/night or a jet lag type of schedule. The latter mimics the biological clock disruption of people working night shifts. The scientists found that under jet lag conditions, tumors grew faster and more aggressively.
“If you disrupt these genes in every cell of the body, the light cues that you normally receive do not apply,” Papagiannakopoulos said. “It’s a way of taking a molecular hammer and just breaking this clock.”
As reported by the American Psychological Association, no amount of extra sleep in the world can compensate for a messed-up circadian rhythm.
Joseph Takahashi, chair of the Department of Neuroscience at the University of Texas Southwestern Medical Center, noted that although the results are very clear and definitive, further research is needed to confirm the results.
Therefore, Papagiannakopoulos is now investigating whether circadian disruptions also affect other cancer types, and whether or not a broken clock can be exploited as a potential drug target or cancer prevention strategy.
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