Lung Adenocarcinoma Distally Rewires Hepatic Circadian Homeostasis

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 home...

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Bibliographic Details
Main Authors: Masri, Selma (Author), Kinouchi, Kenichiro (Author), Liu, Yu (Author), Cervantes, Marlene (Author), Baldi, Pierre (Author), Sassone-Corsi, Paolo (Author), Papagiannakopoulos, Thales (Contributor), Jacks, Tyler E. (Contributor)
Other Authors: Massachusetts Institute of Technology. Department of Comparative Media Studies (Contributor)
Format: Article
Language:English
Published: Elsevier, 2018-06-25T15:33:40Z.
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Online Access:Get fulltext
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100 1 0 |a Masri, Selma  |e author 
100 1 0 |a Massachusetts Institute of Technology. Department of Comparative Media Studies  |e contributor 
100 1 0 |a Papagiannakopoulos, Thales  |e contributor 
100 1 0 |a Jacks, Tyler E.  |e contributor 
700 1 0 |a Kinouchi, Kenichiro  |e author 
700 1 0 |a Liu, Yu  |e author 
700 1 0 |a Cervantes, Marlene  |e author 
700 1 0 |a Baldi, Pierre  |e author 
700 1 0 |a Sassone-Corsi, Paolo  |e author 
700 1 0 |a Papagiannakopoulos, Thales  |e author 
700 1 0 |a Jacks, Tyler E.  |e author 
245 0 0 |a Lung Adenocarcinoma Distally Rewires Hepatic Circadian Homeostasis 
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520 |a 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. 
655 7 |a Article 
773 |t Cell