Lung Adenocarcinoma Distally Rewires Hepatic Circadian Homeostasis

Selma Masri, Thales Papagiannakopoulos, Kenichiro Kinouchi, Yu Liu, Marlene Cervantes, Pierre Baldi, Tyler Jacks, Paolo Sassone-Corsi

Research output: Contribution to journalArticlepeer-review

185 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)896-909
Number of pages14
Issue number4
Publication statusPublished - 2016 May 5
Externally publishedYes

ASJC Scopus subject areas

  • General Biochemistry,Genetics and Molecular Biology


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