Integrative modelling of the influence of MAPK network on cancer cell fate decision.

The Mitogen-Activated Protein Kinase (MAPK) network consists of tightly interconnected signalling pathways involved in diverse cellular processes, such as cell cycle, survival, apoptosis and differentiation. Although several studies reported the involvement of these signalling cascades in cancer der...

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Autores principales:	Luca Grieco, Laurence Calzone, Isabelle Bernard-Pierrot, François Radvanyi, Brigitte Kahn-Perlès, Denis Thieffry
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/0633aeb0790b4f2580b7c96ecea1953b
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spelling	oai:doaj.org-article:0633aeb0790b4f2580b7c96ecea1953b2021-11-18T05:53:28ZIntegrative modelling of the influence of MAPK network on cancer cell fate decision.1553-734X1553-735810.1371/journal.pcbi.1003286https://doaj.org/article/0633aeb0790b4f2580b7c96ecea1953b2013-10-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24250280/?tool=EBIhttps://doaj.org/toc/1553-734Xhttps://doaj.org/toc/1553-7358The Mitogen-Activated Protein Kinase (MAPK) network consists of tightly interconnected signalling pathways involved in diverse cellular processes, such as cell cycle, survival, apoptosis and differentiation. Although several studies reported the involvement of these signalling cascades in cancer deregulations, the precise mechanisms underlying their influence on the balance between cell proliferation and cell death (cell fate decision) in pathological circumstances remain elusive. Based on an extensive analysis of published data, we have built a comprehensive and generic reaction map for the MAPK signalling network, using CellDesigner software. In order to explore the MAPK responses to different stimuli and better understand their contributions to cell fate decision, we have considered the most crucial components and interactions and encoded them into a logical model, using the software GINsim. Our logical model analysis particularly focuses on urinary bladder cancer, where MAPK network deregulations have often been associated with specific phenotypes. To cope with the combinatorial explosion of the number of states, we have applied novel algorithms for model reduction and for the compression of state transition graphs, both implemented into the software GINsim. The results of systematic simulations for different signal combinations and network perturbations were found globally coherent with published data. In silico experiments further enabled us to delineate the roles of specific components, cross-talks and regulatory feedbacks in cell fate decision. Finally, tentative proliferative or anti-proliferative mechanisms can be connected with established bladder cancer deregulations, namely Epidermal Growth Factor Receptor (EGFR) over-expression and Fibroblast Growth Factor Receptor 3 (FGFR3) activating mutations.Luca GriecoLaurence CalzoneIsabelle Bernard-PierrotFrançois RadvanyiBrigitte Kahn-PerlèsDenis ThieffryPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Computational Biology, Vol 9, Iss 10, p e1003286 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Luca Grieco Laurence Calzone Isabelle Bernard-Pierrot François Radvanyi Brigitte Kahn-Perlès Denis Thieffry Integrative modelling of the influence of MAPK network on cancer cell fate decision.
description	The Mitogen-Activated Protein Kinase (MAPK) network consists of tightly interconnected signalling pathways involved in diverse cellular processes, such as cell cycle, survival, apoptosis and differentiation. Although several studies reported the involvement of these signalling cascades in cancer deregulations, the precise mechanisms underlying their influence on the balance between cell proliferation and cell death (cell fate decision) in pathological circumstances remain elusive. Based on an extensive analysis of published data, we have built a comprehensive and generic reaction map for the MAPK signalling network, using CellDesigner software. In order to explore the MAPK responses to different stimuli and better understand their contributions to cell fate decision, we have considered the most crucial components and interactions and encoded them into a logical model, using the software GINsim. Our logical model analysis particularly focuses on urinary bladder cancer, where MAPK network deregulations have often been associated with specific phenotypes. To cope with the combinatorial explosion of the number of states, we have applied novel algorithms for model reduction and for the compression of state transition graphs, both implemented into the software GINsim. The results of systematic simulations for different signal combinations and network perturbations were found globally coherent with published data. In silico experiments further enabled us to delineate the roles of specific components, cross-talks and regulatory feedbacks in cell fate decision. Finally, tentative proliferative or anti-proliferative mechanisms can be connected with established bladder cancer deregulations, namely Epidermal Growth Factor Receptor (EGFR) over-expression and Fibroblast Growth Factor Receptor 3 (FGFR3) activating mutations.
format	article
author	Luca Grieco Laurence Calzone Isabelle Bernard-Pierrot François Radvanyi Brigitte Kahn-Perlès Denis Thieffry
author_facet	Luca Grieco Laurence Calzone Isabelle Bernard-Pierrot François Radvanyi Brigitte Kahn-Perlès Denis Thieffry
author_sort	Luca Grieco
title	Integrative modelling of the influence of MAPK network on cancer cell fate decision.
title_short	Integrative modelling of the influence of MAPK network on cancer cell fate decision.
title_full	Integrative modelling of the influence of MAPK network on cancer cell fate decision.
title_fullStr	Integrative modelling of the influence of MAPK network on cancer cell fate decision.
title_full_unstemmed	Integrative modelling of the influence of MAPK network on cancer cell fate decision.
title_sort	integrative modelling of the influence of mapk network on cancer cell fate decision.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/0633aeb0790b4f2580b7c96ecea1953b
work_keys_str_mv	AT lucagrieco integrativemodellingoftheinfluenceofmapknetworkoncancercellfatedecision AT laurencecalzone integrativemodellingoftheinfluenceofmapknetworkoncancercellfatedecision AT isabellebernardpierrot integrativemodellingoftheinfluenceofmapknetworkoncancercellfatedecision AT francoisradvanyi integrativemodellingoftheinfluenceofmapknetworkoncancercellfatedecision AT brigittekahnperles integrativemodellingoftheinfluenceofmapknetworkoncancercellfatedecision AT denisthieffry integrativemodellingoftheinfluenceofmapknetworkoncancercellfatedecision
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Integrative modelling of the influence of MAPK network on cancer cell fate decision.

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