Interactions of circadian clock genes with the hallmarks of cancer

Ortega-Campos, Sara M.; Verdugo‐Sivianes, Eva M.; Amiama-Roig, Ana; Blanco, José Ramón; Carnero, Amancio

doi:10.1016/j.bbcan.2023.188900

Cited by 15 publications

(9 citation statements)

References 189 publications

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“…Disruptions to the circadian rhythm in the environment seem to enhance the establishment of distant metastases. These factors can produce inflammatory cytokines and neurotransmitters, activate macrophages, decrease immunological responses, and cause angiogenesis [ 84 ].…”

Section: Cancer Genetics: the Mechanismsmentioning

confidence: 99%

The Relationship between Circadian Rhythm and Cancer Disease

Munteanu,

Turti,

Achim

et al. 2024

IJMS

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The circadian clock regulates biological cycles across species and is crucial for physiological activities and biochemical reactions, including cancer onset and development. The interplay between the circadian rhythm and cancer involves regulating cell division, DNA repair, immune function, hormonal balance, and the potential for chronotherapy. This highlights the importance of maintaining a healthy circadian rhythm for cancer prevention and treatment. This article investigates the complex relationship between the circadian rhythm and cancer, exploring how disruptions to the internal clock may contribute to tumorigenesis and influence cancer progression. Numerous databases are utilized to conduct searches for articles, such as NCBI, MEDLINE, and Scopus. The keywords used throughout the academic archives are “circadian rhythm”, ”cancer”, and ”circadian clock”. Maintaining a healthy circadian cycle involves prioritizing healthy sleep habits and minimizing disruptions, such as consistent sleep schedules, reduced artificial light exposure, and meal timing adjustments. Dysregulation of the circadian clock gene and cell cycle can cause tumor growth, leading to the need to regulate the circadian cycle for better treatment outcomes. The circadian clock components significantly impact cellular responses to DNA damage, influencing cancer development. Understanding the circadian rhythm’s role in tumor diseases and their therapeutic targets is essential for treating and preventing cancer. Disruptions to the circadian rhythm can promote abnormal cell development and tumor metastasis, potentially due to immune system imbalances and hormonal fluctuations.

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Section: Cancer Genetics: the Mechanismsmentioning

confidence: 99%

The Relationship between Circadian Rhythm and Cancer Disease

Munteanu,

Turti,

Achim

et al. 2024

IJMS

View full text Add to dashboard Cite

show abstract

“…Moreover, T98G cultures showed signi cant differences in cell viability across time when cells were treated with SR9009 (synthetic REV-ERB agonists), an effect that was further potentiated when SR9009 was combined with Bortezomib (Wagner et al 2019). Environmental alterations, genetic mutations, or changes in circadian gene expression can disrupt the normal functioning of the circadian machinery and increase the risk of cancer occurrence and progression (reviewed in (Sulli et al 2019;Ortega-Campos et al 2023)). In fact, the International Agency for Research on Cancer (IARC) classi ed "shift work leading to a circadian disruption" as a probable human carcinogen (Group 2A) (Stevens et al 2011).…”

Section: Introductionmentioning

confidence: 99%

Pharmacological modulation of the cytosolic oscillator affects glioblastoma cell biology

Wagner,

Guido

2024

Preprint

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The circadian system is a conserved time-keeping machinery that regulates a wide range of processes such as sleep/wake, feeding/fasting, and activity/rest cycles to coordinate behavior and physiology. Circadian disruption can be a contributing factor in the development of metabolic diseases, inflammatory disorders, and higher risk of cancer. Glioblastoma (GBM) is a highly aggressive grade 4 brain tumor that is resistant to conventional therapies and has a poor prognosis after diagnosis, with a median survival of only 12–15 months. GBM cells kept in culture were shown to contain a functional circadian oscillator. In seeking more efficient therapies with lower side effects, we evaluated the pharmacological modulation of the circadian clock by targeting the cytosolic kinases glycogen synthase kinase-3 (GSK-3) and casein kinase ε/δ (CK1ε/δ) with specific inhibitors (CHIR99022 and PF670462, respectively), the cryptochrome protein stabilizer (KL001), or circadian disruption after Per2 knockdown expression in GBM-derived cells. CHIR99022-treated cells had a significant effect on cell viability, clock protein expression, migration, and cell cycle distribution. Moreover, cultures exhibited higher levels of reactive oxygen species and alterations in lipid droplet content after GSK-3 inhibition compared to control cells. The combined treatment of CHIR99022 with temozolomide was found to improve the effect on cell viability compared to temozolomide therapy alone. Per2 disruption affected both GBM migration and cell cycle progression. Overall, our results suggest that pharmacological modulation or molecular clock disruption severely affects glioblastoma cell biology.

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“…It comprises a central pacemaker in the suprachiasmatic nucleus (SCN) and peripheral clocks in the individual cells and is crucial for maintaining body homoeostasis. The circadian clock controls almost all physiological processes and its disruption is linked to diseases such as cancer and metabolic disorders 8 . The clock is driven by a core set of elements, the core-clock, interconnected in translational and transcriptional feedback/feed-forward loops 9 (Fig.…”

Section: Introductionmentioning

confidence: 99%

Molecular mechanisms of tumour development in glioblastoma: an emerging role for the circadian clock

Nelson,

Relógio

2024

npj Precis. Onc.

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Glioblastoma is one of the most lethal cancers with current therapeutic options lacking major successes. This underlines the necessity to understand glioblastoma biology on other levels and use these learnings for the development of new therapeutic concepts. Mounting evidence in the field of circadian medicine points to a tight interplay between disturbances of the circadian system and glioblastoma progression. The circadian clock, an internal biological mechanism governing numerous physiological processes across a 24-h cycle, also plays a pivotal role in regulationg key cellular functions, including DNA repair, cell cycle progression, and apoptosis. These processes are integral to tumour development and response to therapy. Disruptions in circadian rhythms can influence tumour growth, invasion, and response to treatment in glioblastoma patients. In this review, we explore the robust association between the circadian clock, and cancer hallmarks within the context of glioblastoma. We further discuss the impact of the circadian clock on eight cancer hallmarks shown previously to link the molecular clock to different cancers, and summarize the putative role of clock proteins in circadian rhythm disturbances and chronotherapy in glioblastoma. By unravelling the molecular mechanisms behind the intricate connections between the circadian clock and glioblastoma progression, researchers can pave the way for the identification of potential therapeutic targets, the development of innovative treatment strategies and personalized medicine approaches. In conclusion, this review underscores the significant influence of the circadian clock on the advancement and understanding of future therapies in glioblastoma, ultimately leading to enhanced outcomes for glioblastoma patients.

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Interactions of circadian clock genes with the hallmarks of cancer

Cited by 15 publications

References 189 publications

The Relationship between Circadian Rhythm and Cancer Disease

The Relationship between Circadian Rhythm and Cancer Disease

Pharmacological modulation of the cytosolic oscillator affects glioblastoma cell biology

Molecular mechanisms of tumour development in glioblastoma: an emerging role for the circadian clock

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