The results of a new study seem to suggest that the circadian clock—with its role in metabolism, DNA repair, and cell cycle—might act as a tumor suppressor. The paper was published yesterday in the journal PLOS Biology.
While previous observational studies have seemed to offer evidence that circadian clock disruption may be linked to cancer development, further analysis at the molecular level is needed to confirm these findings.
The current study involved perturbing the proteins RAS, INK4A and ARF in mouse embryonic fibroblasts. RAS is known to be inappropriately activated in a quarter of all tumors, while INK4a and ARF are both known to be cancer suppressors. When Ink4a and ARF were knocked out in mouse fibroblasts, cross talk was observed between the circadian clock and the cell cycle and increased cell proliferation was observed, indicating that dysregulation of the core clock might work as an enhancer of RAS-mediated cell cycle regulation.
These findings appear to suggest that the circadian clock may work as a tumor suppressor and that cancerous cells may find ways to circumvent circadian control. The results could have important implications for determining another biological cancer marker and for adding chronotherapy, adjustment of a patient’s sleep and wake cycles, to future cancer treatment plans.
Image: New research reveals that a link between two biological cycles - the circadian rhythm (top left) and the cell cycle (top right), mediated by several key regulatory proteins (center) - may play a role in the progression and treatment of cancer. Thus changing the length of the "day" (bottom left) can influence the proliferation of cells (bottom right). Image caption: Angela Relógio, adapted by Roland Roberts.