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Circadian Rhythm Disruption Promotes Lung Tumorigenesis
Thales Papagiannakopoulos1, Matthew R Bauer1, Shawn M Davidson2
1David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Cell Metabolism
|August 2, 2016
Summary
Disrupting circadian rhythms, the body's 24-hour biological cycles, accelerates lung cancer growth and progression. Maintaining circadian rhythm homeostasis is crucial for tumor suppression and better cancer prognosis.
Area of Science:
- Chronobiology
- Cancer Biology
- Molecular Oncology
Background:
- Circadian rhythms govern essential biological processes, including cell division and metabolism, which are critical in cancer.
- Disruption of circadian rhythms, such as through shift work, is linked to increased cancer risk and poorer outcomes, suggesting a tumor-suppressive role for circadian homeostasis.
Purpose of the Study:
- To investigate the impact of circadian rhythm disruption on lung tumorigenesis using a genetically engineered mouse model.
- To elucidate the cell-autonomous roles of core circadian clock genes (Per2 and Bmal1) in lung cancer development and progression.
Main Methods:
- Utilized a genetically engineered mouse model of lung adenocarcinoma.
- Induced circadian rhythm disruption through physiologic perturbation (jet lag) and genetic mutation of central circadian clock components.
- Analyzed effects on survival, tumor growth, progression, gene expression (c-Myc), proliferation, and metabolic pathways.
Main Results:
- Both jet lag and genetic disruption of circadian clocks significantly decreased survival and promoted lung tumor growth and progression.
- The core circadian genes Per2 and Bmal1 exhibited cell-autonomous tumor-suppressive functions.
- Loss of central clock components resulted in elevated c-Myc expression, increased cell proliferation, and metabolic dysregulation.
Conclusions:
- Systemic and somatic disruption of circadian rhythms significantly contribute to the progression of lung cancer.
- Circadian rhythm disruption impairs tumor suppression, highlighting the importance of maintaining circadian homeostasis in cancer prevention and treatment.
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