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Circadian disruption: from mouse models to molecular mechanisms and cancer therapeutic targets
Yu Wang1, Haidong Guo2,3, Feng He4
1Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
Abstract:
The circadian clock is a timekeeping system for numerous biological rhythms that contribute to the regulation of numerous homeostatic processes in humans. Disruption of circadian rhythms influences physiology and behavior and is associated with adverse health outcomes, especially cancer. However, the underlying molecular mechanisms of circadian disruption-associated cancer initiation and development remain unclear. It is essential to construct good circadian disruption models to uncover and validate the detailed molecular clock framework of circadian disruption in cancer development and progression. Mouse models are the most widely used in circadian studies due to their relatively small size, fast reproduction cycle, easy genome manipulation, and economic practicality. Here, we reviewed the current mouse models of circadian disruption, including suprachiasmatic nuclei destruction, genetic engineering, light disruption, sleep deprivation, and other lifestyle factors in our understanding of the crosstalk between circadian rhythms and oncogenic signaling, as well as the molecular mechanisms of circadian disruption that promotes cancer growth. We focused on the discoveries made with the nocturnal mouse, diurnal human being, and cell culture and provided several circadian rhythm-based cancer therapeutic strategies.
Insights
Circadian clock disruption promotes cancer by unclear molecular mechanisms. Mouse models are crucial for understanding this link and developing new cancer therapies based on circadian rhythms.
Area of Science:
- Chronobiology
- Cancer Biology
- Translational Medicine
Background:
- The circadian clock regulates human physiology and behavior.
- Circadian rhythm disruption is linked to adverse health outcomes, particularly cancer.
- Molecular mechanisms connecting circadian disruption to cancer remain largely unknown.
Purpose of the Study:
- To review current mouse models for studying circadian disruption in cancer.
- To explore the molecular mechanisms underlying circadian disruption-induced cancer.
- To identify potential circadian rhythm-based cancer therapeutic strategies.
Main Methods:
- Review of existing literature on mouse models of circadian disruption.
- Analysis of studies involving suprachiasmatic nuclei destruction, genetic engineering, light disruption, and sleep deprivation.
- Examination of research on nocturnal mice, diurnal humans, and cell cultures.
Main Results:
- Mouse models are valuable tools for investigating circadian disruption and cancer.
- Circadian disruption influences oncogenic signaling pathways.
- Specific molecular mechanisms linking circadian disruption to cancer promotion have been elucidated through these models.
Conclusions:
- Understanding circadian disruption's role in cancer is essential for developing novel therapies.
- Mouse models provide critical insights into the circadian clock's influence on cancer development.
- Circadian rhythm-based strategies offer promising avenues for cancer treatment.
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