title: Coupling between the Circadian Clock and Cell Cycle Oscillators: Implication for Healthy Cells and Malignant Growth.
abstract: Uncontrolled cell proliferation is one of the key features leading to cancer. Seminal works in chronobiology have revealed that disruption of the circadian timing system in mice, either by surgical, genetic, or environmental manipulation, increased tumor development. In humans, shift work is a risk factor for cancer. Based on these observations, the link between the circadian clock and cell cycle has become intuitive. But despite identification of molecular connections between the two processes, the influence of the clock on the dynamics of the cell cycle has never been formally observed. Recently, two studies combining single live cell imaging with computational methods have shed light on robust coupling between clock and cell cycle oscillators. We recapitulate here these novel findings and integrate them with earlier results in both healthy and cancerous cells. Moreover, we propose that the cell cycle may be synchronized or slowed down through coupling with the circadian clock, which results in reduced tumor growth. More than ever, systems biology has become instrumental to understand the dynamic interaction between the circadian clock and cell cycle, which is critical in cellular coordination and for diseases such as cancer.
authors.affiliation: Circadian Systems Biology, CNRS, INSERM, Institut de Biologie Valrose, Université Nice Sophia Antipolis , Nice , France.
authors.forename: Celine
authors.initials: C
authors.lastname: Feillet
authors.affiliation: Department of Genetics, Erasmus University Medical Center , Rotterdam , Netherlands.
authors.forename: Gijsbertus T J
authors.initials: GT
authors.lastname: van der Horst
authors.affiliation: Cancer Chronotherapy Unit, University of Warwick , Coventry , UK.
authors.forename: Francis
authors.initials: F
authors.lastname: Levi
authors.affiliation: Systems Biology Centre, University of Warwick , Coventry , UK.
authors.forename: David A
authors.initials: DA
authors.lastname: Rand
authors.affiliation: Circadian Systems Biology, CNRS, INSERM, Institut de Biologie Valrose, Université Nice Sophia Antipolis , Nice , France.
authors.forename: Franck
authors.initials: F
authors.lastname: Delaunay
keywords: cancer; cell cycle; circadian desynchrony; coupling; mathematical modeling