Padala2017- ERK, PI3K/Akt and Wnt signalling network (bRaf mutated)

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Short description
Padala2017- ERK, PI3K/Akt and Wnt signalling network (bRaf mutated)
Crosstalk model of the ERK, Wnt and Akt signalling pathways with bRaf mutation

This model is described in the article:

Padala RR, Karnawat R, Viswanathan SB, Thakkar AV, Das AB.
Mol Biosyst 2017 May; 13(5): 830-840

Abstract:

Perturbations in molecular signaling pathways are a result of genetic or epigenetic alterations, which may lead to malignant transformation of cells. Despite cellular robustness, specific genetic or epigenetic changes of any gene can trigger a cascade of failures, which result in the malfunctioning of cell signaling pathways and lead to cancer phenotypes. The extent of cellular robustness has a link with the architecture of the network such as feedback and feedforward loops. Perturbation in components within feedback loops causes a transition from a regulated to a persistently activated state and results in uncontrolled cell growth. This work represents the mathematical and quantitative modeling of ERK, PI3K/Akt, and Wnt/?-catenin signaling crosstalk to show the dynamics of signaling responses during genetic and epigenetic changes in cancer. ERK, PI3K/Akt, and Wnt/?-catenin signaling crosstalk networks include both intra and inter-pathway feedback loops which function in a controlled fashion in a healthy cell. Our results show that cancerous perturbations of components such as EGFR, Ras, B-Raf, PTEN, and components of the destruction complex cause extreme fragility in the network and constitutively activate inter-pathway positive feedback loops. We observed that the aberrant signaling response due to the failure of specific network components is transmitted throughout the network via crosstalk, generating an additive effect on cancer growth and proliferation.

This model is hosted on BioModels Database and identified by: BIOMD0000000653.

To cite BioModels Database, please use: Chelliah V et al. BioModels: ten-year anniversary. Nucl. Acids Res. 2015, 43(Database issue):D542-8.

To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

Format
SBML (L2V4)
Related Publication
  • Cancerous perturbations within the ERK, PI3K/Akt, and Wnt/β-catenin signaling network constitutively activate inter-pathway positive feedback loops.
  • Karnawat R, Das AB
  • Molecular bioSystems , 5/ 2017 , Volume 13 , Issue 5 , pages: 830-840
  • Department of Biotechnology, National Institute of Technology Warangal, Warangal, Telangana 506004, India. bikasasim@gmail.com asimbikas@nitw.ac.in.
  • Perturbations in molecular signaling pathways are a result of genetic or epigenetic alterations, which may lead to malignant transformation of cells. Despite cellular robustness, specific genetic or epigenetic changes of any gene can trigger a cascade of failures, which result in the malfunctioning of cell signaling pathways and lead to cancer phenotypes. The extent of cellular robustness has a link with the architecture of the network such as feedback and feedforward loops. Perturbation in components within feedback loops causes a transition from a regulated to a persistently activated state and results in uncontrolled cell growth. This work represents the mathematical and quantitative modeling of ERK, PI3K/Akt, and Wnt/β-catenin signaling crosstalk to show the dynamics of signaling responses during genetic and epigenetic changes in cancer. ERK, PI3K/Akt, and Wnt/β-catenin signaling crosstalk networks include both intra and inter-pathway feedback loops which function in a controlled fashion in a healthy cell. Our results show that cancerous perturbations of components such as EGFR, Ras, B-Raf, PTEN, and components of the destruction complex cause extreme fragility in the network and constitutively activate inter-pathway positive feedback loops. We observed that the aberrant signaling response due to the failure of specific network components is transmitted throughout the network via crosstalk, generating an additive effect on cancer growth and proliferation.
Contributors
Emma Fairbanks, Rahuman Sheriff

Metadata information

isDerivedFrom
BioModels Database BIOMD0000000623
BioModels Database BIOMD0000000033
BioModels Database BIOMD0000000149
is
BioModels Database MODEL1708290000
BioModels Database BIOMD0000000653
isDescribedBy
PubMed 28367561
PubMed 21391741
hasTaxon
Taxonomy Homo sapiens
unknownQualifier
Mathematical Modelling Ontology Ordinary differential equation model
hasPart
KEGG Pathway MAPK signaling pathway
KEGG Pathway Wnt signaling pathway
Gene Ontology MAPK cascade
KEGG Pathway PI3K-Akt signaling pathway
Curation status
Curated
Name Description Size Actions

Model files

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Additional files

BIOMD0000000653.m Auto-generated Octave file 38.63 KB Preview | Download
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BIOMD0000000653-biopax3.owl Auto-generated BioPAX (Level 3) 190.31 KB Preview | Download
BIOMD0000000653.svg Auto-generated Reaction graph (SVG) 145.40 KB Preview | Download
BIOMD0000000653.vcml Auto-generated VCML file 948.00 bytes Preview | Download
BIOMD0000000653-biopax2.owl Auto-generated BioPAX (Level 2) 113.27 KB Preview | Download
BIOMD0000000653.sci Auto-generated Scilab file 17.32 KB Preview | Download
BIOMD0000000653_urn.xml Auto-generated SBML file with URNs 305.39 KB Preview | Download
BIOMD0000000653.png Auto-generated Reaction graph (PNG) 682.99 KB Preview | Download

  • Model originally submitted by : Emma Fairbanks
  • Submitted: 29-Aug-2017 14:41:51
  • Last Modified: 21-Mar-2019 16:15:28
Revisions
  • Version: 3 public model Download this version
    • Submitted on: 21-Mar-2019 16:15:28
    • Submitted by: Rahuman Sheriff
    • With comment: MAMO term qualifier updated from isDescribedBy to hasProperty
  • Version: 2 public model Download this version
    • Submitted on: 20-Sep-2017 11:50:19
    • Submitted by: Emma Fairbanks
    • With comment: Current version of Padala2017- ERK, PI3K/Akt and Wnt signalling network (bRaf mutated)
  • Version: 1 public model Download this version
    • Submitted on: 29-Aug-2017 14:41:51
    • Submitted by: Emma Fairbanks
    • With comment: Original import of Padala2017- ERK, PI3K/Akt and Wnt signalling network (bRaf mutated)
Curator's comment:
(added: 20 Sep 2017, 11:31:08, updated: 20 Sep 2017, 11:31:08)
Figures 3 F of the reference publication has been reproduced. The model as such reproduces the plots corresponding to the mutated brad condition (Purple line). The blue line and black line corresponds to the simulation in the presence (W=1) and absence (W=0) of Wnt from normal condition model (BIOMD0000000648). The simulations where performed using Copasi 4.19 (Build 140) and the plots were obtained using Matlab R2014b.