Modeling TGF-β signaling pathway in epithelial-mesenchymal transition

The epithelial-mesenchymal transition (EMT) consists in a morphological change in epithelial cells characterized by the loss of the cell adhesion and the acquisition of mesenchymal phenotype. This process plays a crucial role in the embryonic development and in regulating the tissue homeostasis in t...

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Main Authors: Pasquale Laise, Duccio Fanelli, Pietro Lió, Annarosa Arcangeli
Format: Article
Language:English
Published: AIP Publishing LLC 2012-03-01
Series:AIP Advances
Online Access:http://dx.doi.org/10.1063/1.3697962
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author Pasquale Laise
Duccio Fanelli
Pietro Lió
Annarosa Arcangeli
author_facet Pasquale Laise
Duccio Fanelli
Pietro Lió
Annarosa Arcangeli
author_sort Pasquale Laise
collection DOAJ
description The epithelial-mesenchymal transition (EMT) consists in a morphological change in epithelial cells characterized by the loss of the cell adhesion and the acquisition of mesenchymal phenotype. This process plays a crucial role in the embryonic development and in regulating the tissue homeostasis in the adult, but it proves also fundamental for the development of cancer metastasis. Experimental evidences have shown that the EMT depends on the TGF-β signaling pathway, which in turn regulates the transcriptional cellular activity. In this work, a dynamical model of the TGF-β pathway is proposed and calibrated versus existing experimental data on lung cancer A549 cells. The analysis combines Bayesian Markov Chain Monte Carlo (MCMC) and standard Ordinary Differential Equations (ODEs) techniques to interpolate the gene expression data via an iterative adjustments of the parameters involved. The kinetic of the Smad proteins phosphorylation, as predicted within the model is found in excellent agreement with available experiments, an observation that confirms the adequacy of the proposed mathematical picture.
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spelling doaj.art-c6dbc7c4d9a24177b1443b3232801e3c2022-12-21T19:56:36ZengAIP Publishing LLCAIP Advances2158-32262012-03-0121011201011201-1110.1063/1.3697962083201ADVModeling TGF-β signaling pathway in epithelial-mesenchymal transitionPasquale Laise0Duccio Fanelli1Pietro Lió2Annarosa Arcangeli3CSDC Centro Interdipartimentale per lo Studio di Dinamiche Complesse and INFN, University of Florence, ItalyCSDC Centro Interdipartimentale per lo Studio di Dinamiche Complesse and INFN, University of Florence, ItalyComputer Laboratory, University of Cambridge, 15 JJ Thompson Avenue, CB03FD Cambridge, United KingdomDipartimento di Patologia e Oncologia Sperimentali, University of Florence, Istituto Toscano Tumori, Florence, ItalyThe epithelial-mesenchymal transition (EMT) consists in a morphological change in epithelial cells characterized by the loss of the cell adhesion and the acquisition of mesenchymal phenotype. This process plays a crucial role in the embryonic development and in regulating the tissue homeostasis in the adult, but it proves also fundamental for the development of cancer metastasis. Experimental evidences have shown that the EMT depends on the TGF-β signaling pathway, which in turn regulates the transcriptional cellular activity. In this work, a dynamical model of the TGF-β pathway is proposed and calibrated versus existing experimental data on lung cancer A549 cells. The analysis combines Bayesian Markov Chain Monte Carlo (MCMC) and standard Ordinary Differential Equations (ODEs) techniques to interpolate the gene expression data via an iterative adjustments of the parameters involved. The kinetic of the Smad proteins phosphorylation, as predicted within the model is found in excellent agreement with available experiments, an observation that confirms the adequacy of the proposed mathematical picture.http://dx.doi.org/10.1063/1.3697962
spellingShingle Pasquale Laise
Duccio Fanelli
Pietro Lió
Annarosa Arcangeli
Modeling TGF-β signaling pathway in epithelial-mesenchymal transition
AIP Advances
title Modeling TGF-β signaling pathway in epithelial-mesenchymal transition
title_full Modeling TGF-β signaling pathway in epithelial-mesenchymal transition
title_fullStr Modeling TGF-β signaling pathway in epithelial-mesenchymal transition
title_full_unstemmed Modeling TGF-β signaling pathway in epithelial-mesenchymal transition
title_short Modeling TGF-β signaling pathway in epithelial-mesenchymal transition
title_sort modeling tgf β signaling pathway in epithelial mesenchymal transition
url http://dx.doi.org/10.1063/1.3697962
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AT pietrolio modelingtgfbsignalingpathwayinepithelialmesenchymaltransition
AT annarosaarcangeli modelingtgfbsignalingpathwayinepithelialmesenchymaltransition