title: Surprisal analysis characterizes the free energy time course of cancer cells undergoing epithelial-to-mesenchymal transition.
abstract: The epithelial-to-mesenchymal transition (EMT) initiates the invasive and metastatic behavior of many epithelial cancers. Mechanisms underlying EMT are not fully known. Surprisal analysis of mRNA time course data from lung and pancreatic cancer cells stimulated to undergo TGF-β1-induced EMT identifies two phenotypes. Examination of the time course for these phenotypes reveals that EMT reprogramming is a multistep process characterized by initiation, maturation, and stabilization stages that correlate with changes in cell metabolism. Surprisal analysis characterizes the free energy time course of the expression levels throughout the transition in terms of two state variables. The landscape of the free energy changes during the EMT for the lung cancer cells shows a stable intermediate state. Existing data suggest this is the previously proposed maturation stage. Using a single-cell ATP assay, we demonstrate that the TGF-β1-induced EMT for lung cancer cells, particularly during the maturation stage, coincides with a metabolic shift resulting in increased cytosolic ATP levels. Surprisal analysis also characterizes the absolute expression levels of the mRNAs and thereby examines the homeostasis of the transcription system during EMT.
authors.affiliation: Institute for Molecular Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA 90095;
authors.forename: Sohila
authors.initials: S
authors.lastname: Zadran
authors.affiliation: The Fritz Haber Research Center, The Hebrew University, Jerusalem 91904, Israel; and.
authors.forename: Rameshkumar
authors.initials: R
authors.lastname: Arumugam
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, and.
authors.forename: Harvey
authors.initials: H
authors.lastname: Herschman
authors.affiliation: Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, and.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Phelps
authors.affiliation: The Fritz Haber Research Center, The Hebrew University, Jerusalem 91904, Israel; and Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, and Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095 rafi@fh.huji.ac.il.
authors.forename: R D
authors.initials: RD
authors.lastname: Levine
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D045744:Cell Line, Tumor; D003600:Cytosol / Q000378:metabolism; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D063990:Gene Ontology; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000473:pathology*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013816:Thermodynamics; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology
chemical_list: D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D000255:Adenosine Triphosphate
keywords: cellular thermodynamics; free energy landscape; maximal entropy; microarray; transcriptions expression profile