Molecular Links between the Circadian Clock and the Cell Cycle

Farshadi, Elham Aïda; Horst, Gijsbertus T. J. van der; Chaves, Inês

doi:10.1016/j.jmb.2020.04.003

Cited by 109 publications

(96 citation statements)

References 102 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Previously, it has been demonstrated that clock signaling is downregulated in CS exposed mice, linked to an impairment of anti-oxidant defense mechanisms 45 and Rev-erbα has been shown as an key regulator of inflammatory response in lung injury models [16][17][18]46 Furthermore, we found that CS exposure upregulated pathways associated with cell cycle activity in alveolar epithelial progenitors, which could be counteracted by in vivo misoprostol or iloprost treatment. The cell cycle [47][48][49][50][51] is driven by a set of tightly regulated molecular events controlling DNA replication and mitosis with four phases, and each individual cell may require different triggers in order to decide whether to enter proliferation or apoptosis. To further assess alveolar epithelial progenitors under which cell cycle/apoptotic status in response to CS exposure as well as additional PGE2/PGI2 treatments may be the next step to investigate in the future.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

A transcriptomics-guided drug target discovery strategy identifies novel receptor ligands for lung regeneration

Bos

Conlon

et al. 2021

Preprint

View full text Add to dashboard Cite

Currently, there is no pharmacological treatment targeting defective tissue repair in chronic disease. Here we utilized a transcriptomics-guided drug target discovery strategy using gene signatures of smoking-associated chronic obstructive pulmonary disease (COPD) and from mice chronically exposed to cigarette smoke, identifying druggable targets expressed in alveolar epithelial progenitors of which we screened the function in lung organoids. We found several drug targets with regenerative potential of which EP and IP prostanoid receptor ligands had the most significant therapeutic potential in restoring cigarette smoke-induced defects in alveolar epithelial progenitors in vitro and in vivo. Mechanistically, we discovered by using scRNA-sequencing analysis that circadian clock and cell cycle/apoptosis signaling pathways were enriched in alveolar epithelial progenitor cells in COPD patients and in a relevant model of COPD, which was prevented by PGE2 or PGI2 mimetics. Conclusively, specific targeting of EP and IP receptors offers therapeutic potential for injury to repair in COPD.

show abstract

Section: Discussionmentioning

confidence: 99%

“…To further assess alveolar epithelial progenitors under which cell cycle/apoptotic status in response to CS exposure as well as additional PGE2/PGI2 treatments may be the next step to investigate in the future. A link between circadian clock and cell cycle signaling pathways has been proposed 44,50,52 .…”

Section: Discussionmentioning

confidence: 99%

A transcriptomics-guided drug target discovery strategy identifies novel receptor ligands for lung regeneration

Bos

Conlon

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…Some researchers have suggested that the molecular clock is able to "gate", i.e., allow cell cycle progression [158], a concepted that has been challenged [156,157,159]. The molecular clock exerts its effects on the cell cycle either by controlling transcription of key regulatory genes or by protein-protein interaction (reviewed in [160]). In this line, it is not surprising to realize that disruption of the circadian clock is in fact correlated to a loss of cell cycle progression control, often seen in cancer [161] [162][163][164].…”

Section: Cellular Processesmentioning

confidence: 99%

The circadian clock and metabolic homeostasis: entangled networks

Assis

Oster

2021

Cell. Mol. Life Sci.

View full text Add to dashboard Cite

The circadian clock exerts an important role in systemic homeostasis as it acts a keeper of time for the organism. The synchrony between the daily challenges imposed by the environment needs to be aligned with biological processes and with the internal circadian clock. In this review, it is provided an in-depth view of the molecular functioning of the circadian molecular clock, how this system is organized, and how central and peripheral clocks communicate with each other. In this sense, we provide an overview of the neuro-hormonal factors controlled by the central clock and how they affect peripheral tissues. We also evaluate signals released by peripheral organs and their effects in the central clock and other brain areas. Additionally, we evaluate a possible communication between peripheral tissues as a novel layer of circadian organization by reviewing recent studies in the literature. In the last section, we analyze how the circadian clock can modulate intracellular and tissue-dependent processes of metabolic organs. Taken altogether, the goal of this review is to provide a systemic and integrative view of the molecular clock function and organization with an emphasis in metabolic tissues.

show abstract

“…Cross talk between circadian oscillators and the cell cycle is well established (Farshadi et al, 2020). Dysregulation of the cell cycle is a key driver of increased proliferative capacity.…”

Section: Mechanism Overview -Cell Cyclementioning

confidence: 99%

Cancer clocks in tumourigenesis: the p53 pathway and beyond

Stephenson

Usselmann

Tergaonkar

et al. 2021

Endocrine-Related Cancer

View full text Add to dashboard Cite

Circadian rhythms regulate a vast array of physiological and cellular processes, as well as the hormonal milieu, to keep our cells synchronised to the light-dark cycle. Epidemiologic studies have implicated circadian disruption in the development of breast and other cancers, and numerous clock genes are dysregulated in human tumours. Here we review the evidence that circadian rhythms, when altered at the molecular level, influence cancer growth. We also note some common pitfalls in circadian-cancer research and how they might be avoided to maximise comparable results and minimise misleading data. Studies of circadian gene mutant mice, and human cancer models in vitro and in vivo, demonstrate that clock genes can impact tumourigenesis. Clock genes influence important cancer related pathways, ranging from p53-mediated apoptosis to cell cycle progression. Confusingly, clock dysfunction can be both pro- or anti- tumourigenic in a model and cell type specific manner. Due to this duality, there is no canonical mechanism for clock interaction with tumourigenic pathways. To understand the role of the circadian clock in patients’ tumours requires analysis of the molecular clock status compared to healthy tissue. Novel mathematical approaches are under development, but this remains largely aspirational, and is hampered by a lack of temporal information in publicly available datasets. Current evidence broadly supports the notion that the circadian clock is important for cancer biology. More work is necessary to develop an overarching model of this connection. Future studies would do well to analyse the clock network in addition to alterations in single clock genes.

show abstract

Molecular Links between the Circadian Clock and the Cell Cycle

Cited by 109 publications

References 102 publications

A transcriptomics-guided drug target discovery strategy identifies novel receptor ligands for lung regeneration

A transcriptomics-guided drug target discovery strategy identifies novel receptor ligands for lung regeneration

The circadian clock and metabolic homeostasis: entangled networks

Cancer clocks in tumourigenesis: the p53 pathway and beyond

Contact Info

Product

Resources

About