title: Lung Adenocarcinoma Distally Rewires Hepatic Circadian Homeostasis.
abstract: 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.
authors.affiliation: Center for Epigenetics and Metabolism, INSERM Unit 904, Department of Biological Chemistry, University of California, Irvine (UCI), Irvine, CA 92697, USA.
authors.forename: Selma
authors.initials: S
authors.lastname: Masri
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Thales
authors.initials: T
authors.lastname: Papagiannakopoulos
authors.affiliation: Center for Epigenetics and Metabolism, INSERM Unit 904, Department of Biological Chemistry, University of California, Irvine (UCI), Irvine, CA 92697, USA.
authors.forename: Kenichiro
authors.initials: K
authors.lastname: Kinouchi
authors.affiliation: Institute for Genomics and Bioinformatics, Department of Computer Science, UCI, Irvine, CA 92697, USA.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Center for Epigenetics and Metabolism, INSERM Unit 904, Department of Biological Chemistry, University of California, Irvine (UCI), Irvine, CA 92697, USA.
authors.forename: Marlene
authors.initials: M
authors.lastname: Cervantes
authors.affiliation: Institute for Genomics and Bioinformatics, Department of Computer Science, UCI, Irvine, CA 92697, USA.
authors.forename: Pierre
authors.initials: P
authors.lastname: Baldi
authors.affiliation: Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
authors.forename: Tyler
authors.initials: T
authors.lastname: Jacks
authors.affiliation: Center for Epigenetics and Metabolism, INSERM Unit 904, Department of Biological Chemistry, University of California, Irvine (UCI), Irvine, CA 92697, USA. Electronic address: psc@uci.edu.
authors.forename: Paolo
authors.initials: P
authors.lastname: Sassone-Corsi
mesh_terms: D000230:Adenocarcinoma / Q000503:physiopathology*; D000077192:Adenocarcinoma of Lung; D000818:Animals; D057906:Circadian Clocks; D016207:Cytokines / Q000235:genetics; D005947:Glucose / Q000378:metabolism; D006706:Homeostasis; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000503:physiopathology*; D008175:Lung Neoplasms / Q000503:physiopathology*; D051379:Mice; D015398:Signal Transduction
chemical_list: D016207:Cytokines; D007328:Insulin; D005947:Glucose