Ticking time bombs: connections between circadian clocks and cancer.

Katja A. Lamia

doi:10.12688/f1000research.11770.1

Abstract

Connections between mammalian circadian and cell division cycles have been postulated since the early 20th century, and epidemiological and genetic studies have linked disruption of circadian clock function to increased risk of several types of cancer. In the past decade, it has become clear that circadian clock components influence cell growth and transformation in a cell-autonomous manner. Furthermore, several molecular mechanistic connections have been described in which clock proteins participate in sensing DNA damage, modulating DNA repair, and influencing the ubiquitination and degradation of key players in oncogenesis (c-MYC) and tumor suppression (p53).

Highlights

Connections between mammalian cell division cycles and time of day have been postulated since the early 20th century when Mrs C.E
Many epidemiological studies have demonstrated that disruption of circadian rhythms caused by shift work increases the risk of several cancers[11,12,13,14,15,16,17,18], and the size of the effect is correlated with the duration and severity of circadian disruption
Unlike other tumor types, skin cancers were recently found to be reduced among night shift workers[19] and this might be due to reduced sun exposure

Summary

Introduction

Connections between mammalian cell division cycles and time of day have been postulated since the early 20th century when Mrs C.E. Additional studies investigating the effects of clock gene disruptions in tumor models driven by a variety of genetic manipulations (and in myriad cell types) are needed to improve our understanding of how circadian disruption impacts different types of cancers. A handful of recent studies demonstrated that exposing mice to light cycles engineered to impose a state of “chronic jet lag”, mimicking the experience of rotational shift work, increased tumor formation in breast, lung, and liver cancer models[26,41,55,56,57]. While some of the transcriptional changes in Cry2−/− cells can be explained by the unique role of CRY2 in modulating c-MYC protein stability (see below), further investigation will be required to understand the mechanism(s) by which mammalian CRYs participate in the DNA damage response.

Fortuyn-van Leijden CE

Pittendrigh CS