Circadian Rhythm Disruption Promotes Lung Tumorigenesis
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nihms851645.pdf
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Author(s)
Papagiannakopoulos, Thales
Bauer, Matthew R.
Davidson, Shawn M.
Heimann, Megan Kristianne
Subbaraj, Lakshmipriya
Bhutkar, Arjun
Bartlebaugh, Jordan M. E.
Vander Heiden, Matthew G.
Jacks, Tyler E.
Date Issued
July 2018
Journal
Cell Metabolism
Publisher
Elsevier
Citation
Papagiannakopoulos, Thales et al. “Circadian Rhythm Disruption Promotes Lung Tumorigenesis.” Cell Metabolism 24, 2 (August 2016): 324–331 © 2016 Elsevier Inc
Version
Author's final manuscript
Abstract
Circadian rhythms are 24-hr oscillations that control a variety of biological processes in living systems, including two hallmarks of cancer, cell division and metabolism. Circadian rhythm disruption by shift work is associated with greater risk for cancer development and poor prognosis, suggesting a putative tumor-suppressive role for circadian rhythm homeostasis. Using a genetically engineered mouse model of lung adenocarcinoma, we have characterized the effects of circadian rhythm disruption on lung tumorigenesis. We demonstrate that both physiologic perturbation (jet lag) and genetic mutation of the central circadian clock components decreased survival and promoted lung tumor growth and progression. The core circadian genes Per2 and Bmal1 were shown to have cell-autonomous tumor-suppressive roles in transformation and lung tumor progression. Loss of the central clock components led to increased c-Myc expression, enhanced proliferation, and metabolic dysregulation. Our findings demonstrate that both systemic and somatic disruption of circadian rhythms contribute to cancer progression.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.CMET.2016.07.001
