Altered circadian rhythm seen to increase aggressive tumor growth.
A recent study found that night shift workers are more likely to develop cancer due to a disruption in the body’s circadian rhythm.
A study published in Cell Metabolism found that disrupting the circadian rhythm can inhibit 2 tumor suppressor genes and can lead to tumor growth. The circadian rhythm is composed of 20,000 nerve cells in the brain called the suprachiasmatic nucleus (SCN), which is located in the hypothalamus.
The SCN receives information from the retina about levels of lightness and darkness, and then sends this information to other cells, according to the study. Researchers found that the gene Bmal1 activates Per2, which then turns on processes regulated by the circadian rhythm such as cell division and metabolism.
The proteins that are encoded by these genes fluctuate throughout the day but stop if light and dark cycles are disrupted, according to the study.
"Cells need the light cue, which is like a reset button for the clock,” said lead author of the study Thales Papagiannakopoulos, PhD. “When you lose that cue, you lose the normal rhythms in every cell in your body.”
In the study, researchers used mouse models of non-small cell lung cancer, and analyzed how different dark and light schedules affected gene activity and tumor growth. In first group, the mice were exposed to a normal light and dark schedules consisting of 12 hours of each.
In the second group, mice were on a jet lag schedule where they were exposed to an additional 8 hours of light every 2 to 3 days. The jet lag group experienced circadian rhythm disruption similar to humans who work night shifts.
Researchers found that mice on the jet lag schedule had faster and more aggressive tumor growth. Next, researchers removed Bmal1 and Per2 from mice, and then exposed them to normal light and dark schedules. They discovered rapid tumor growth.
“If you disrupt these genes in every cell of the body, the light cues that you normally receive do not apply,” Dr Papagiannakopoulos said. “It's a way of taking a molecular hammer and just breaking this clock.”
Investigators discovered that Bmal1 and Per2 genes regulate the production of c-myc, a protein that promotes cancer growth. They then examined samples of human lung tumors, and found low levels of Bmal1 and Per2.
They also discovered low levels of other genes that regulate circadian rhythm. Researchers plan to study whether this may affect other cancers, as well.
“We demonstrate that both physiologic perturbation (jet lag) and genetic mutation of the central circadian clock components decreased survival and promoted lung tumor growth and progression,” Dr Papagiannakopoulos concluded. “Our findings demonstrate that both systemic and somatic disruption of circadian rhythms contribute to cancer progression.”