Cancer and the Circadian Clock

Shafi, Ayesha A.; Knudsen, Karen E.

doi:10.1158/0008-5472.can-19-0566

Cited by 168 publications

(176 citation statements)

References 135 publications

Supporting

Mentioning

158

Contrasting

Unclassified

Order By: Relevance

“…The circadian clock controls diverse cellular processes, including the cell cycle, DNA damage response and apoptosis, by regulating genes, such as p16 , p21 , Cyclin D1 , Wee1 and p53. 38,91–93 These molecular links further support the notion that disruption of circadian regulation promotes cancer phenotypes, such as rapid proliferation, impairment of DNA repair and resistance to apoptosis. Given the potential significance of dedifferentiation processes in carcinogenesis, it is critical to understand the effects of global epigenetic changes on the circadian clock and how the circadian clock is regulated in developing cancer cells (Fig.…”

Section: Impact Of Circadian Clock Disruption On Cancer Developmentsupporting

confidence: 52%

Circadian clock and cancer: From a viewpoint of cellular differentiation

2020

View full text Add to dashboard Cite

Abbreviations & Acronyms AML = acute myeloid leukemia ccg = clock-controlled gene DNMT1 = DNA methyltransferase 1 E19 = embryonic day 19 ES = embryonic stem iPS = induced pluripotent stem MEF = mouse embryonic fibroblast MRT = malignant rhabdoid tumor OSKM = Oct3/4, Sox2, Klf4 and c-Myc Per2 Luc = Per2::Luciferase SCN = suprachiasmatic nucleus SMG = submandibular gland TTFL = transcriptionaltranslational feedback loop UPR = unfolded protein response Correspondence: KazuhiroAbstract: The circadian clock controls and adapts diverse physiological and behavioral processes according to Earth's 24-h cycle of environmental changes. The master pacemaker of the mammalian circadian clock resides in the hypothalamic suprachiasmatic nucleus, but almost all cells throughout the body show circadian oscillations in gene expression patterns and associated functions. Recent studies have shown that the circadian clock gradually develops during embryogenesis. Embryonic stem cells and induced pluripotent stem cells do not show circadian oscillations of gene expression, but gradually develop circadian clock oscillation during differentiation; thus, the developmental program of circadian clock emergence appears closely associated with cellular differentiation. Like embryonic stem cells, certain cancer cell types also lack the circadian clock. Given this similarity between embryonic stem cells and cancer cells, interest is growing in the contributions of circadian clock dysfunction to dedifferentiation and cancer development. In this review, we summarize recent advances in our understanding of circadian clock emergence during ontogenesis, and discuss possible associations with cellular differentiation and carcinogenesis. Considering the multiple physiological functions of circadian rhythms, circadian abnormalities might contribute to a host of diseases, including cancer. Insights on circadian function could lead to the identification of biomarkers for cancer diagnosis and prognosis, as well as novel targets for treatment. Hierarchical organization of the mammalian circadian clockMost organisms have evolved an intrinsic circadian clock to adapt physiological functions to the planet's 24-h environmental cycles. In mammals, the circadian clock controls such physiological and behavioral functions as sleep-wake cycles, metabolism, hormonal secretion, body temperature, immune responses and neuronal functions. 1,2 The master pacemaker of the mammalian circadian clock resides in the SCN of the hypothalamus. A subset of SCN neurons receive a clock-resetting light signal from the retinohypothalamic tract and communicate with other SCN cells to maintain robust circadian oscillations of neuronal activity. These neuronal oscillations in turn synchronize other peripheral oscillators throughout the body through neuronal and hormonal signaling pathways. 3,4 At the cellular and molecular levels, the circadian clock is comprised of a set of core clock genes functionally organized into TTFLs that generate cell-autonomous circadian oscillations in gene ex...

show abstract

Section: Impact Of Circadian Clock Disruption On Cancer Developmentsupporting

confidence: 52%

Circadian clock and cancer: From a viewpoint of cellular differentiation

2020

View full text Add to dashboard Cite

show abstract

“…Circadian factors including CRY1 hold diverse functions across multiple cancer types, with underpinning mechanisms poorly defined 10 . CRY1 harbors known functions in lower eukaryotes as an effector of both transcriptional control and resolution of UVinduced DNA damage; this latter function manifests through functional domains conferring photolyase activity with~40-60% similarity of protein structure to evolutionarily conserved photolyases 10,17,18 . While CRY1 somatic alterations and gene amplifications occur in several tumor types, ( Supplementary Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Here, analyses of advanced PCa unexpectedly identified CRY1 (cryptochrome 1), a transcriptional coregulator associated with the circadian clock 10 as a tumor specific, AR-mediated, critical effector of DNA repair that is deregulated in metastatic PCa patients and associated with poor outcome. Several epidemiological studies indicate that disruptions in circadian rhythm, such as jet lag, shift work, sleep disruption, and suppression of melatonin by exposure to light at night are all associated with increased risk of PCa, breast cancer, and colon cancer [4][5][6][7][8] .…”

mentioning

confidence: 99%

The circadian cryptochrome, CRY1, is a pro-tumorigenic factor that rhythmically modulates DNA repair

et al. 2021

Self Cite

View full text Add to dashboard Cite

Mechanisms regulating DNA repair processes remain incompletely defined. Here, the circadian factor CRY1, an evolutionally conserved transcriptional coregulator, is identified as a tumor specific regulator of DNA repair. Key findings demonstrate that CRY1 expression is androgen-responsive and associates with poor outcome in prostate cancer. Functional studies and first-in-field mapping of the CRY1 cistrome and transcriptome reveal that CRY1 regulates DNA repair and the G2/M transition. DNA damage stabilizes CRY1 in cancer (in vitro, in vivo, and human tumors ex vivo), which proves critical for efficient DNA repair. Further mechanistic investigation shows that stabilized CRY1 temporally regulates expression of genes required for homologous recombination. Collectively, these findings reveal that CRY1 is hormone-induced in tumors, is further stabilized by genomic insult, and promotes DNA repair and cell survival through temporal transcriptional regulation. These studies identify the circadian factor CRY1 as pro-tumorigenic and nominate CRY1 as a new therapeutic target.

show abstract

“…Immunologists may be interested in the extent to which the various white blood cell types vary across the diurnal cycle (Pick et al, 2019), how molecular processes related to immune function oscillate within each of these cell types, and how far these intracellular or intercellular rhythms are directly modulated by local circadian clocks (Baxter and Ray, 2019; Downton et al, 2019). Oncologists are interested in rhythmicity in tumors and how circadian phase assessment may allow the most effective timing of chemo- or radiotherapies (Shafi and Knudsen, 2019; Shuboni-Mulligan et al, 2019). Neurologists and psychiatrists are interested in circadian rhythms in mood, seizures, and neurodegeneration (Logan and McClung, 2019; Khan et al, 2018; Leng et al, 2019; Pavlova et al, 2009; Lucey et al, 2017).…”

Section: A Biomarker For Circadian Phase Amplitude and Period Of Whmentioning

confidence: 99%

Novel Approaches for Assessing Circadian Rhythmicity in Humans: A Review

Dijk

Duffy

2020

J Biol Rhythms

View full text Add to dashboard Cite

The temporal organization of molecular and physiological processes is driven by environmental and behavioral cycles as well as by self-sustained molecular circadian oscillators. Quantification of phase, amplitude, period, and disruption of circadian oscillators is essential for understanding their contribution to sleep-wake disorders, social jet lag, interindividual differences in entrainment, and the development of chrono-therapeutics. Traditionally, assessment of the human circadian system, and the output of the SCN in particular, has required collection of long time series of univariate markers such as melatonin or core body temperature. Data were collected in specialized laboratory protocols designed to control for environmental and behavioral influences on rhythmicity. These protocols are time-consuming, expensive, and not practical for assessing circadian status in patients or in participants in epidemiologic studies. Novel approaches for assessment of circadian parameters of the SCN or peripheral oscillators have been developed. They are based on machine learning or mathematical model-informed analyses of features extracted from 1 or a few samples of high-dimensional data, such as transcriptomes, metabolomes, long-term simultaneous recording of activity, light exposure, skin temperature, and heart rate or in vitro approaches. Here, we review whether these approaches successfully quantify parameters of central and peripheral circadian oscillators as indexed by gold standard markers. Although several approaches perform well under entrained conditions when sleep occurs at night, the methods either perform worse in other conditions such as shift work or they have not been assessed under any conditions other than entrainment and thus we do not yet know how robust they are. Novel approaches for the assessment of circadian parameters hold promise for circadian medicine, chrono-therapeutics, and chrono-epidemiology. There remains a need to validate these approaches against gold standard markers, in individuals of all sexes and ages, in patient populations, and, in particular, under conditions in which behavioral cycles are displaced.

show abstract

Cancer and the Circadian Clock

Cited by 168 publications

References 135 publications

Circadian clock and cancer: From a viewpoint of cellular differentiation

Circadian clock and cancer: From a viewpoint of cellular differentiation

The circadian cryptochrome, CRY1, is a pro-tumorigenic factor that rhythmically modulates DNA repair

Novel Approaches for Assessing Circadian Rhythmicity in Humans: A Review

Contact Info

Product

Resources

About