Molecular crosstalk between circadian clock and cancer and therapeutic implications

Qu, Meng

doi:10.3389/fnut.2023.1143001

Cited by 8 publications

(3 citation statements)

References 76 publications

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“…39 It has often been postulated that the molecular explanation for enhanced cancer risk in shift workers will be related to mechanisms that underlie altered tumorigenesis in models of genetic deletion of clock components. [40][41][42][43][44][45][46] While disruption of environmental light cycles alters the expression of circadian clock components, it does not fully suppress them, and thus is very different from the impact of genetic deletion.…”

Section: Discussionmentioning

confidence: 99%

Circadian disruption does not alter tumorigenesis in a mouse model of lymphoma

Mello,

Pariollaud,

Lamia

2023

F1000Res

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Background: Disruption of natural light cycles, as experienced by shift workers, is linked to enhanced cancer incidence. Several mouse models of cancer develop more severe disease when exposed to irregular light/dark cycles, supporting the connection between circadian disruption and increased cancer risk. Cryptochrome 2 (CRY2), a repressive component of the molecular circadian clock, facilitates turnover of the oncoprotein c-MYC, one mechanism that may link the molecular clock to tumorigenesis. In Eμ-MYC mice, which express transgenic c-MYC in B cells and develop aggressive lymphomas and leukemia, global Cry2 deletion reduces survival and enhances tumor formation. Lighting conditions that mimic the disruption experienced by shift workers dampen Cry2 transcripts in peripheral tissues of C57BL/6J mice. Although it is milder than homozygous deletion of Cry2, we hypothesized that reduced Cry2 rhythmicity could alter MYC protein accumulation and contribute to enhanced cancer risk caused by circadian disruption. We tested this hypothesis in MYC-driven lymphoma. Methods: We housed Eμ-MYC mice in light-tight boxes set to either control (continuous cycles of 12-hours of light followed by 12-hours of dark, LD12:12) or chronic jetlag (eight-hour light phase advances every two to three days, CJL) lighting conditions and assessed the impact of disrupted light cycles on survival and tumor formation in Eμ-MYC mice. Results: Environmental disruption of circadian rhythms did not alter tumor location, tumor growth, or survival in Eμ-MYC mice. Conclusions: Dampened rhythms of Cry2 following disruption of circadian light exposures is milder than deletion of Cry2. The lack of phenotype caused by altered circadian gene expression in contrast to enhanced tumorigenesis caused by homozygous deletion of Cry2 suggests that CRY2 dosage impacts this model. Importantly, these findings indicate that increased cancer risk associated with circadian disruption arises from one or more mechanisms that are not recapitulated here, and may be different in distinct tumor types.

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Section: Discussionmentioning

confidence: 99%

Circadian disruption does not alter tumorigenesis in a mouse model of lymphoma

Mello,

Pariollaud,

Lamia

2023

F1000Res

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“…Given the diverse involvement of the core clock components in cancer management, it is advantageous for future research to create cancer-specific techniques to enhance traditional first-line regimens. A deeper knowledge of clock–cancer interactions will help to develop blood or tissue-based biomarkers for molecular classification of cancer patients who may respond differently to clock-targeting therapy [ 232 ].…”

Section: The Relationship Between the Circadian Clock And Cancer Trea...mentioning

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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“…This self-sustained internal system orchestrates fundamental physiological processes, including the sleep-wake cycle, energy metabolism, immune function, cognitive and physical performance, as well as cell proliferation and tumorigenesis[ 2 , 3 ]. Additionally, it contributes to the adaptation of organisms to environmental changes, thereby maintaining systematic and tissue homeostasis[ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Circadian rhythm disruption and endocrine-related tumors

Savvidis,

Kallistrou,

Kouroglou

et al. 2024

World J Clin Oncol

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This review delved into the intricate relationship between circadian clocks and physiological processes, emphasizing their critical role in maintaining homeostasis. Orchestrated by interlocked clock genes, the circadian timekeeping system regulates fundamental processes like the sleep-wake cycle, energy metabolism, immune function, and cell proliferation. The central oscillator in the hypothalamic suprachiasmatic nucleus synchronizes with light-dark cycles, while peripheral tissue clocks are influenced by cues such as feeding times. Circadian disruption, linked to modern lifestyle factors like night shift work, correlates with adverse health outcomes, including metabolic syndrome, cardiovascular diseases, infections, and cancer. We explored the molecular mechanisms of circadian clock genes and their impact on metabolic disorders and cancer pathogenesis. Specific associations between circadian disruption and endocrine tumors, spanning breast, ovarian, testicular, prostate, thyroid, pituitary, and adrenal gland cancers, are highlighted. Shift work is associated with increased breast cancer risk, with PER genes influencing tumor progression and drug resistance. CLOCK gene expression correlates with cisplatin resistance in ovarian cancer, while factors like aging and intermittent fasting affect prostate cancer. Our review underscored the intricate interplay between circadian rhythms and cancer, involving the regulation of the cell cycle, DNA repair, metabolism, immune function, and the tumor microenvironment. We advocated for integrating biological timing into clinical considerations for personalized healthcare, proposing that understanding these connections could lead to novel therapeutic approaches. Evidence supports circadian rhythm-focused therapies, particularly chronotherapy, for treating endocrine tumors. Our review called for further research to uncover detailed connections between circadian clocks and cancer, providing essential insights for targeted treatments. We emphasized the importance of public health interventions to mitigate lifestyle-related circadian disruptions and underscored the critical role of circadian rhythms in disease mechanisms and therapeutic interventions.

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Molecular crosstalk between circadian clock and cancer and therapeutic implications

Cited by 8 publications

References 76 publications

Circadian disruption does not alter tumorigenesis in a mouse model of lymphoma

Circadian disruption does not alter tumorigenesis in a mouse model of lymphoma

The Relationship between Circadian Rhythm and Cancer Disease

Circadian rhythm disruption and endocrine-related tumors

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