Timing is everything: New discoveries in circadian rhythms provide insight into cancer treatment
In a recent paper in Science Signaling, affiliated faculty, associate professor of cell and microbiology Carla Finkielstein, of the Department of Biological Sciences, and her collaborators identified an alternative mechanism to control circadian rhythms in normal cells that is driven by oncoproteins.
This discovery places molecules involved in monitoring and calibrating the response of cells to genomic damage at the center of the machinery driving circadian rhythms.
Anyone who has ever experienced jetlag is familiar with circadian rhythms. Various processes in the human body are governed by circadian rhythms, even down to the individual cell. These processes are tightly controlled by a variety of molecular mechanisms and feedback loops that help the body self-regulate in response to external cues like sunlight and temperature.
Researchers are now discovering that molecules usually implicated in protecting us from cancer initiation and progression are directly involved in regulating the function of our daily circadian rhythms. Not only that, but this molecular interplay seems to regulate how well our body responds to therapeutic modalities seldom delivered to treat certain diseases, such as cancer.
While healthy cells share a circadian rhythm with the rest of the body, tumors often have a different rhythm than the healthy cells surrounding them. Tumors divide differently than healthy cells and at different times. Like a person singing out of tune within a chorus, that one difference can ultimately wreck the entire melody. Or in this case, the healthy functions of cells.
“We know that our cells experience over 10,000 mutations a day,” said Finkielstein. “These are usually mitigated by a repair system comprised of a host of protein interactions. However, only a handful of mutations, three to six depending on the type of cancer, are needed for malignant cells to get a foothold. And if one of these mutations occurs in the repair system, then the chances for cancer increase dramatically.”