Time Matters: Does Our Biological Clock Keep Cancer at Bay?


Source: Charité-Medical University of Berlin, Germany

Summary: New research suggests that a link between two biological cycles – circadian rhythm and the cell cycle, mediated by many key regulatory proteins, may play a role in the progression and treatment of cancer.


In mammals, the circadian clock runs in sync with environmental light-dark cycles and controls the punctual regulation of biological processes, which, in turn, affect physiology and behavior. But many diseases specifically cancer can disrupt the internal biological clock and cause it to run amok. The cell cycle is the series of events that take place in a cell leading to its division to produce two daughter cells. In most of the cancers, the cell cycle becomes hyperactive or dysfunctional which enables the tumor cells to multiply uncontrollably. Researchers from the Charité-Medical University of Berlin found a link between these two biological cycles – circadian clock and the cell cycle, mediated by many key regulatory proteins, may play a role in the progression and treatment of cancer. The study findings were published in the journal PLOS.

circadian rhythm and the cell cycle play a role in the progression and treatment of cancer. 

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 (centre) – 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). Credit: Angela Relógio, adapted by Roland Roberts.

The research team found that upon perturbations of a protein called RAS is inappropriately activated in about 25% of all human tumors and two other proteins called INK4a and ARF are in a cross-talk between the circadian clock and the cell cycle. They showed that RAS which controls the cell cycle also controls the circadian rhythms, and exerts its effect on the circadian clock through INK4A and ARF. Their research highlights the significant role of circadian clock as a modulator of cell fate decisions and further supports the function of the circadian clock as a cancer-preventing mechanism. The findings are in support with the recent studies that propose the use of chronotherapy (A behavioral technique in which sleeping and waking times are adjusted in an attempt to reset the patient’s biological clock).

Dr. Angela Relógio said,  “Based on our results, it seems to us that the clock is likely to act as a tumour 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.”


More Information: El-Athman R et al, “The Ink4a/Arf locus operates as a regulator of the circadian clock modulating RAS activity” PLOS Biology (2017).

 doi.org/10.1371/journal.pbio.2002940


 

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