Oxygen and Carbon Dioxide Rhythms Are Circadian Clock Controlled and Differentially Directed by Behavioral Signals

Adamovich, Yaarit; Ladeuix, Benjamin; Sobel, Jonathan; Manella, Gal; Neufeld-Cohen, Adi; Assadi, Mohammad H.; Golik, Marina; Kuperman, Yael; Tarasiuk, Ariel; Koeners, Maarten P.; Asher, Gad

doi:10.1016/j.cmet.2019.01.007

Cited by 78 publications

(87 citation statements)

References 55 publications

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“…The low pH seems to dampen circadian oscillations rather than desynchronize [17]. Decreasing the ambient carbon dioxide concentration from 5% to 1% phase-shifted the circadian rhythmicity of BMAL1 in NIH3T3 cells by 5 h [108]. It was proposed that the shift could be caused by a change in pH, or as a result of carbon dioxide directly affecting the circadian clock, which has been previously hypothesized [109].…”

Section: Disruption Of Tumor Circadian Rhythms By Microenvironmental mentioning

confidence: 94%

The Cancer Clock Is (Not) Ticking: Links between Circadian Rhythms and Cancer

et al. 2019

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Circadian rhythms regulate many physiological and behavioral processes, including sleep, metabolism and cell division, which have a 24-h oscillation pattern. Rhythmicity is generated by a transcriptional–translational feedback loop in individual cells, which are synchronized by the central pacemaker in the brain and external cues. Epidemiological and clinical studies indicate that disruption of these rhythms can increase both tumorigenesis and cancer progression. Environmental changes (shift work, jet lag, exposure to light at night), mutations in circadian regulating genes, and changes to clock gene expression are recognized forms of disruption and are associated with cancer risk and/or cancer progression. Experimental data in animals and cell cultures further supports the role of the cellular circadian clock in coordinating cell division and DNA repair, and disrupted cellular clocks accelerate cancer cell growth. This review will summarize studies linking circadian disruption to cancer biology and explore how such disruptions may be further altered by common characteristics of tumors including hypoxia and acidosis. We will highlight how circadian rhythms might be exploited for cancer drug development, including how delivery of current chemotherapies may be enhanced using chronotherapy. Understanding the role of circadian rhythms in carcinogenesis and tumor progression will enable us to better understand causes of cancer and how to treat them.

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Section: Disruption Of Tumor Circadian Rhythms By Microenvironmental mentioning

confidence: 94%

The Cancer Clock Is (Not) Ticking: Links between Circadian Rhythms and Cancer

et al. 2019

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“…[ 61 ] Interestingly, hypoxia may itself act as a (tissue‐specific) zeitgeber to coordinate tissue clock phase coherence across the body. [ 62,63 ]…”

Section: Tissue Clock Knockouts Yield Various Phenotypesmentioning

confidence: 99%

The Tissue Clock Network: Driver and Gatekeeper of Circadian Physiology

Harder

Oster

2020

BioEssays

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In mammals, a network of cellular circadian clocks organizes physiology and behavior along the 24-h day cycle. The traditional hierarchical model of circadian clock organization with a central pacemaker and peripheral slave oscillators has recently been challenged by studies combining tissue-specific mouse mutants with transcriptome analyses. First, a surprisingly small number of tissue rhythms are lost when only local clocks are ablated and, second, transcriptional circadian rhythms appear to be regulated by a complex mix of local and systemic factors. As reviewed here, these findings suggest a more integrated model of clock network interaction with the central pacemaker as the main source of behavioral and systemic-physiological rhythms and peripheral clocks controlling some local rhythms while at the same time acting as gatekeepers that temporally adjust cellular responses to external stimuli.

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“…Per1 –/– Per2 –/– ( Zheng et al, 2001 ) were back crossed to C57BL/6 ( Adamovich et al, 2019 ) and single Per1 –/– , Per2 –/– , were generated (kindly provided by Gad Asher, WIS). These mice and WT C57Bl/6 controls (ENVIGO RMS, Israel) were maintained under specific-pathogen-free conditions at the Weizmann Institute’s animal facility.…”

Section: Methodsmentioning

confidence: 99%

Stromal Expression of the Core Clock Gene Period 2 Is Essential for Tumor Initiation and Metastatic Colonization

Shaashua

Mayer

Lior

et al. 2020

Front. Cell Dev. Biol.

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The circadian clock regulates diverse physiological processes by maintaining a 24-h gene expression pattern. Genetic and environmental cues that disrupt normal clock rhythms can lead to cancer, yet the extent to which this effect is controlled by the cancer cells versus non-malignant cells in the tumor microenvironment (TME) is not clear. Here we set out to address this question, by selective manipulation of circadian clock genes in the TME. In two different mouse models of cancer we find that expression of the core clock gene Per2 in the TME is crucial for tumor initiation and metastatic colonization, whereas another core gene, Per1 , is dispensable. We further show that loss of Per2 in the TME leads to significant transcriptional changes in response to cancer cell introduction. These changes may contribute to a tumor-suppressive microenvironment. Thus, our work unravels an unexpected protumorigenic role for the core clock gene Per2 in the TME, with potential implications for therapeutic dosing strategies and treatment regimens.

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Oxygen and Carbon Dioxide Rhythms Are Circadian Clock Controlled and Differentially Directed by Behavioral Signals

Cited by 78 publications

References 55 publications

The Cancer Clock Is (Not) Ticking: Links between Circadian Rhythms and Cancer

The Cancer Clock Is (Not) Ticking: Links between Circadian Rhythms and Cancer

The Tissue Clock Network: Driver and Gatekeeper of Circadian Physiology

Stromal Expression of the Core Clock Gene Period 2 Is Essential for Tumor Initiation and Metastatic Colonization

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