Our body clock, or “circadian” clock, normally cycles daily and is synchronized to environmental patterns of light and dark. Cells also have a separate schedule known as the cell cycle, which guides the timing of cell division and multiplication. Both cycles can be disrupted in cancer, and while cell cycle disruption is known to cause uncontrollable cell replication and tumor growth, the relationship between the circadian clock and cancer is less well characterized.
Molecular biologist Angela Relógio was surely fated to work in this area of research, with a surname that means “clock” in Portuguese. With colleagues, she investigated what happened in healthy mouse cells when they perturbed three proteins: the tumor suppressors INK4a and ARF, and RAS, which is inappropriately activated in about a quarter of all human tumors.
The researchers discovered that RAS, which was already known to control the cell cycle, also controls a cell’s circadian clock and exerts its effects via INK4A and ARF. The cross talk they found between the circadian cycle and the cell cycle suggests that the circadian clock may play a role in suppressing cancer, and its disruption may promote carcinogenesis.
Relógio believes her findings suggest “that the clock is likely to act as a tumor suppressor, and that it is of advantage for cancer cells to circumvent circadian control. One cannot stop wondering whether disrupted circadian timing should be included as a next potential hallmark of cancer.”
Some recent studies have proposed the use of chronotherapy in cancer treatment, with patients’ sleep-wake cycles being adjusted in an attempt to reset their biological clocks. These new findings would support the incorporation of the circadian cycle as well as the cell cycle into our understanding and treatment of cancer.
Research Article: El-Athman R, Genov NN, Mazuch J, Zhang K, Yu Y, Fuhr L, et al. (2017) The Ink4a/Arf locus operates as a regulator of the circadian clock modulating RAS activity. PLoS Biol 15(12): e2002940. https://doi.org/10.1371/journal.pbio.2002940
Image Credit: Relógio et al., 2017