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Lung Adenocarcinoma Distally Rewires Hepatic Circadian Homeostasis
Open accessAbstract
The circadian clock controls metabolic and physiological processes through finely tuned molecular mechanisms. The clock is remarkably plastic and adapts to exogenous "zeitgebers," such as light and nutrition. How a pathological condition in a given tissue influences systemic circadian homeostasis in other tissues remains an unanswered question of conceptual and biomedical importance. Here, we show that lung adenocarcinoma operates as an endogenous reorganizer of circadian metabolism. High-throughput transcriptomics and metabolomics revealed unique signatures of transcripts and metabolites cycling exclusively in livers of tumor-bearing mice. Remarkably, lung cancer has no effect on the core clock but rather reprograms hepatic metabolism through altered pro-inflammatory response via the STAT3-Socs3 pathway. This results in disruption of AKT, AMPK, and SREBP signaling, leading to altered insulin, glucose, and lipid metabolism. Thus, lung adenocarcinoma functions as a potent endogenous circadian organizer (ECO), which rewires the pathophysiological dimension of a distal tissue such as the liver. PAPERCLIP.
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“Systemic and tissue-specific disruption of the circadian machinery leads to changes in cellular functions such as cell division and metabolism, both highly relevant to cancer (Bass and Takahashi, 2010; Hanahan and Weinberg, 2011; Masri et al., 2016; Sahar and Sassone-Corsi, 2009).”
From Circadian Rhythm Disruption Promotes Lung Tumorigenesis (2016) · cites this paper as Masri et al., 2016
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“Systemic and tissue-specific disruption of the circadian machinery leads to changes in cellular functions such as cell division and metabolism, both highly relevant to cancer (Bass and Takahashi, 2010; Hanahan and Weinberg, 2011; Masri et al., 2016; Sahar and SassoneCorsi, 2009).”
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Metadata
- Authors
- Masri, S., Papagiannakopoulos, T., Kinouchi, K., Liu, Y., Cervantes, M., Baldi, P., Jacks, T., & Sassone-Corsi, P.
- Affiliations
- Inserm (FR)
- Massachusetts Institute of Technology (US)
- University of California, Irvine (US)
- Howard Hughes Medical Institute (US)
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-05
- Volume
- 165
- Issue
- 4
- Pages
- 896-909
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5373476
- OpenAlex
- W2345890567
- Cited by
- 234
- References
- 67
- Citations by year
- 2026: 10 · 2025: 15 · 2024: 14 · 2023: 17 · 2022: 28 · 2021: 33 · 2020: 25 · 2019: 27 · 2018: 26 · 2017: 24 · 2016: 15
- FWCI
- 19.50
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- eScholarship (California Digital Library) (submittedVersion)
- PMC
- Funders
- National Institute on Aging (R21AG043745)
- National Cancer Institute (P30CA062203)
- National Institute of General Medical Sciences (F32GM097899)
- U.S. National Library of Medicine (R01LM010235)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Circular RNAs in diseases
- Keywords
- lung adenocarcinoma, circadian clock, hepatic metabolism, tumor-bearing liver, pro-inflammatory response, AMPK signaling, Akt signaling, SREBP signaling, insulin metabolism, glucose metabolism, lipid metabolism, circadian transcriptome
- MeSH terms
- Adenocarcinoma of Lung, Adenocarcinoma, Animals, Glucose, Homeostasis, Insulin, Liver, Lung Neoplasms, Signal Transduction, Cytokines, Mice, Circadian Clocks
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