Bidkhori2012 - EGFR signalling in NSCLC

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Model Identifier
BIOMD0000000453
Short description
Bidkhori2012 - EGFR signalling in NSCLC

The paper describes and compares two models on EGFR signalling between normal and NSCLC cells. Moreover, it is shown that ERK (MAPK), STAT and Akt factor's activation pattern are different between normal and NSCLA models. This model corresponds to EGFR signalling in NSCLA cells.

Created by The MathWorks, Inc. SimBiology tool, Version 3.3

This model is described in the article:

Bidkhori G, Moeini A, Masoudi-Nejad A
PloS one [2012, 7(10):e48004]

Abstract:

EGFR signaling plays a very important role in NSCLC. It activates Ras/ERK, PI3K/Akt and STAT activation pathways. These are the main pathways for cell proliferation and survival. We have developed two mathematical models to relate to the different EGFR signaling in NSCLC and normal cells in the presence or absence of EGFR and PTEN mutations. The dynamics of downstream signaling pathways vary in the disease state and activation of some factors can be indicative of drug resistance. Our simulation denotes the effect of EGFR mutations and increased expression of certain factors in NSCLC EGFR signaling on each of the three pathways where levels of pERK, pSTAT and pAkt are increased. Over activation of ERK, Akt and STAT3 which are the main cell proliferation and survival factors act as promoting factors for tumor progression in NSCLC. In case of loss of PTEN, Akt activity level is considerably increased. Our simulation results show that in the presence of erlotinib, downstream factors i.e. pAkt, pSTAT3 and pERK are inhibited. However, in case of loss of PTEN expression in the presence of erlotinib, pAkt level would not decrease which demonstrates that these cells are resistant to erlotinib.

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
  • Modeling of tumor progression in NSCLC and intrinsic resistance to TKI in loss of PTEN expression.
  • Bidkhori G, Moeini A, Masoudi-Nejad A
  • PloS one , 0/ 2012 , Volume 7 , pages: e48004 , PubMed ID: 23133538
  • Laboratory of Systems Biology and Bioinformatics, Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.
  • EGFR signaling plays a very important role in NSCLC. It activates Ras/ERK, PI3K/Akt and STAT activation pathways. These are the main pathways for cell proliferation and survival. We have developed two mathematical models to relate to the different EGFR signaling in NSCLC and normal cells in the presence or absence of EGFR and PTEN mutations. The dynamics of downstream signaling pathways vary in the disease state and activation of some factors can be indicative of drug resistance. Our simulation denotes the effect of EGFR mutations and increased expression of certain factors in NSCLC EGFR signaling on each of the three pathways where levels of pERK, pSTAT and pAkt are increased. Over activation of ERK, Akt and STAT3 which are the main cell proliferation and survival factors act as promoting factors for tumor progression in NSCLC. In case of loss of PTEN, Akt activity level is considerably increased. Our simulation results show that in the presence of erlotinib, downstream factors i.e. pAkt, pSTAT3 and pERK are inhibited. However, in case of loss of PTEN expression in the presence of erlotinib, pAkt level would not decrease which demonstrates that these cells are resistant to erlotinib.
Contributors
Gholamreza Bidkhori

Metadata information

is
BioModels Database MODEL1304020001
BioModels Database BIOMD0000000453
isDerivedFrom
BioModels Database BIOMD0000000093
PubMed 16687399
BioModels Database BIOMD0000000048
BioModels Database BIOMD0000000049
BioModels Database BIOMD0000000094
BioModels Database BIOMD0000000205
BioModels Database BIOMD0000000019
PubMed 20459599
PubMed 14751248
BioModels Database BIOMD0000000009
isDescribedBy
PubMed 23133538
hasTaxon
hasProperty
Mathematical Modelling Ontology Ordinary differential equation model
Human Disease Ontology non-small cell lung carcinoma

Curation status
Curated


Tags
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Model files

BIOMD0000000453_url.xml SBML L2V4 representation of Bidkhori2012 - EGFR signalling in NSCLC 309.31 KB Preview | Download

Additional files

BIOMD0000000453.pdf Auto-generated PDF file 1.17 MB Preview | Download
BIOMD0000000453.sci Auto-generated Scilab file 126.51 KB Preview | Download
BIOMD0000000453.xpp Auto-generated XPP file 58.78 KB Preview | Download
BIOMD0000000453-biopax3.owl Auto-generated BioPAX (Level 3) 524.03 KB Preview | Download
BIOMD0000000453-biopax2.owl Auto-generated BioPAX (Level 2) 304.38 KB Preview | Download
BIOMD0000000453.m Auto-generated Octave file 105.88 KB Preview | Download
BIOMD0000000453.vcml Auto-generated VCML file 423.33 KB Preview | Download
BIOMD0000000453.svg Auto-generated Reaction graph (SVG) 640.97 KB Preview | Download
BIOMD0000000453.png Auto-generated Reaction graph (PNG) 5.25 MB Preview | Download
BIOMD0000000453_urn.xml Auto-generated SBML file with URNs 304.08 KB Preview | Download

  • Model originally submitted by : Gholamreza Bidkhori
  • Submitted: Apr 2, 2013 12:05:32 PM
  • Last Modified: Oct 21, 2014 5:02:35 PM
Revisions
  • Version: 2 public model Download this version
    • Submitted on: Oct 21, 2014 5:02:35 PM
    • Submitted by: Gholamreza Bidkhori
    • With comment: Current version of Bidkhori2012 - EGFR signalling in NSCLC
  • Version: 1 public model Download this version
    • Submitted on: Apr 2, 2013 12:05:32 PM
    • Submitted by: Gholamreza Bidkhori
    • With comment: Original import of NSCLC EGFR signaling model_ By: Gholamreza Bidkhori

(*) You might be seeing discontinuous revisions as only public revisions are displayed here. Any private revisions unpublished model revision of this model will only be shown to the submitter and their collaborators.

Legends
: Variable used inside SBML models


Species
Reactions
Reactions Rate Parameters
mwf430a579_ecbf_48ba_80c2_06e455808f2a + mw9dcaa655_a755_426e_a3fa_1ad7c3c45575 => mw1093b3af_1864_4ba3_a541_6009a9921282; mwf430a579_ecbf_48ba_80c2_06e455808f2a, mw9dcaa655_a755_426e_a3fa_1ad7c3c45575, mw1093b3af_1864_4ba3_a541_6009a9921282 mwbb727dc5_30e8_45f4_9d15_3b34be5c1e93*mwf430a579_ecbf_48ba_80c2_06e455808f2a*mw9dcaa655_a755_426e_a3fa_1ad7c3c45575-mw7ae1ee96_563e_4684_bc9a_8f4ef373620e*mw1093b3af_1864_4ba3_a541_6009a9921282 mwbb727dc5_30e8_45f4_9d15_3b34be5c1e93=0.1; mw7ae1ee96_563e_4684_bc9a_8f4ef373620e=0.0015
mwbfcf6773_1915_432c_b1d2_1f246094cc74 + mwf430a579_ecbf_48ba_80c2_06e455808f2a => mwd9462e5b_a272_4b66_ab66_fde9266b1a43; mwbfcf6773_1915_432c_b1d2_1f246094cc74, mwf430a579_ecbf_48ba_80c2_06e455808f2a, mwd9462e5b_a272_4b66_ab66_fde9266b1a43 mwc585e0e4_b7e7_4290_8a6d_10fcd9759a2d*mwbfcf6773_1915_432c_b1d2_1f246094cc74*mwf430a579_ecbf_48ba_80c2_06e455808f2a-mwf44d37d0_fe7f_4e47_bf10_1e734fbc3391*mwd9462e5b_a272_4b66_ab66_fde9266b1a43 mwf44d37d0_fe7f_4e47_bf10_1e734fbc3391=0.05; mwc585e0e4_b7e7_4290_8a6d_10fcd9759a2d=3.0
mw5babe3d5_a9af_4dfd_ac01_35474ef64af2 => mwd784228d_0cb5_468a_ac70_02d8f04b3d9c + mwbfcf6773_1915_432c_b1d2_1f246094cc74 + mwa0349407_8187_48fc_9e94_5698ccc4e06d + mwf430a579_ecbf_48ba_80c2_06e455808f2a + mw31ac308f_da36_4f73_830f_67f3e5b945d9; mw5babe3d5_a9af_4dfd_ac01_35474ef64af2 mw1ddaf9f4_dcab_4dc2_a6fa_5ce85b9d7a3a*mw5babe3d5_a9af_4dfd_ac01_35474ef64af2 mw1ddaf9f4_dcab_4dc2_a6fa_5ce85b9d7a3a=0.0426
mwa98802cb_c977_4fe0_9e67_5000904c2c36 + mwf430a579_ecbf_48ba_80c2_06e455808f2a => mw504578d8_96c3_471f_8a7e_8c14e7535d3d; mwa98802cb_c977_4fe0_9e67_5000904c2c36, mwf430a579_ecbf_48ba_80c2_06e455808f2a, mw504578d8_96c3_471f_8a7e_8c14e7535d3d mwe879a9ac_4b8d_4c9a_a157_a3751761cf63*mwa98802cb_c977_4fe0_9e67_5000904c2c36*mwf430a579_ecbf_48ba_80c2_06e455808f2a-mwa18578d7_236f_4939_baca_52259e38fe15*mw504578d8_96c3_471f_8a7e_8c14e7535d3d mwa18578d7_236f_4939_baca_52259e38fe15=0.1; mwe879a9ac_4b8d_4c9a_a157_a3751761cf63=3.0
mw504578d8_96c3_471f_8a7e_8c14e7535d3d + mwe57c3282_5935_405c_8c0b_7fadb7a5de17 => mw45ab688a_6467_4a3e_a779_2118fa84d69e; mw504578d8_96c3_471f_8a7e_8c14e7535d3d, mwe57c3282_5935_405c_8c0b_7fadb7a5de17, mw45ab688a_6467_4a3e_a779_2118fa84d69e mw289fed85_e6ee_43e6_a69f_77b5f487a452*mw504578d8_96c3_471f_8a7e_8c14e7535d3d*mwe57c3282_5935_405c_8c0b_7fadb7a5de17-mw8768b5c7_b227_4825_aa55_a525b0d915c2*mw45ab688a_6467_4a3e_a779_2118fa84d69e mw289fed85_e6ee_43e6_a69f_77b5f487a452=10.0; mw8768b5c7_b227_4825_aa55_a525b0d915c2=1.0
mw45ab688a_6467_4a3e_a779_2118fa84d69e => mwa8f2e7b2_0927_4ab4_a817_dddc43bb4fa3 + mwa0349407_8187_48fc_9e94_5698ccc4e06d + mwf430a579_ecbf_48ba_80c2_06e455808f2a + mwe57c3282_5935_405c_8c0b_7fadb7a5de17; mw45ab688a_6467_4a3e_a779_2118fa84d69e mwd12a67b3_6d98_40e9_a54b_282a577498eb*mw45ab688a_6467_4a3e_a779_2118fa84d69e mwd12a67b3_6d98_40e9_a54b_282a577498eb=2.661
mwf40d6176_abfc_4a30_886f_83a19fcffc48 => mwfbda4e09_0cbb_49bc_ae69_f88b7a79ed21 + mwa54a9c38_c98b_45e5_8432_4119fb777e44; mwf40d6176_abfc_4a30_886f_83a19fcffc48 mwfc146e94_8070_4727_8416_fb55829068cb*mwf40d6176_abfc_4a30_886f_83a19fcffc48 mwfc146e94_8070_4727_8416_fb55829068cb=0.1434
mwcedf8ecd_67bd_4b91_aa04_d58782dec2a4 => mwf816df4c_4593_4d23_990f_0d7c15ddde5d + mwcc894c94_0ddf_42cc_913e_cdcc4d471d94; mwcedf8ecd_67bd_4b91_aa04_d58782dec2a4 mwa4c71b8d_fb74_465b_b76e_cec4e4c95484*mwcedf8ecd_67bd_4b91_aa04_d58782dec2a4 mwa4c71b8d_fb74_465b_b76e_cec4e4c95484=16.0
mwcc894c94_0ddf_42cc_913e_cdcc4d471d94 + mwd087f76b_65dc_47f1_ba21_c43774457686 => mw35f5adaa_d1c0_433c_817d_76e317f4cb15; mwcc894c94_0ddf_42cc_913e_cdcc4d471d94, mwd087f76b_65dc_47f1_ba21_c43774457686, mw35f5adaa_d1c0_433c_817d_76e317f4cb15 mw254868f8_c9fb_493c_bc1d_807cc83c18e6*mwcc894c94_0ddf_42cc_913e_cdcc4d471d94*mwd087f76b_65dc_47f1_ba21_c43774457686-mw78a41659_4abc_4614_9e83_38cbfe1c5262*mw35f5adaa_d1c0_433c_817d_76e317f4cb15 mw254868f8_c9fb_493c_bc1d_807cc83c18e6=5.0; mw78a41659_4abc_4614_9e83_38cbfe1c5262=0.5
mwf816df4c_4593_4d23_990f_0d7c15ddde5d + mwcc894c94_0ddf_42cc_913e_cdcc4d471d94 => mw6cb74b27_ffef_49bb_8ffb_622d552caa9e; mwf816df4c_4593_4d23_990f_0d7c15ddde5d, mwcc894c94_0ddf_42cc_913e_cdcc4d471d94, mw6cb74b27_ffef_49bb_8ffb_622d552caa9e mwc40b3165_cc16_4f78_86b5_e34f2731dcbb*mwf816df4c_4593_4d23_990f_0d7c15ddde5d*mwcc894c94_0ddf_42cc_913e_cdcc4d471d94-mw8bff2fe0_b582_4020_8f05_83f14451b1c0*mw6cb74b27_ffef_49bb_8ffb_622d552caa9e mw8bff2fe0_b582_4020_8f05_83f14451b1c0=0.033; mwc40b3165_cc16_4f78_86b5_e34f2731dcbb=3.0
mwdf82303e_323f_4c51_a858_56a59233cd98 => mw8f5a7b5c_ca4c_4a4c_85b1_e5d640c426bf + mw7cff9a0e_094d_498e_bf7f_7b162c61d63a; mwdf82303e_323f_4c51_a858_56a59233cd98 mw23e16d40_acbb_4658_a336_be5d0b0dd86a*mwdf82303e_323f_4c51_a858_56a59233cd98 mw23e16d40_acbb_4658_a336_be5d0b0dd86a=7.76
mwbfcf6773_1915_432c_b1d2_1f246094cc74 + mw7cff9a0e_094d_498e_bf7f_7b162c61d63a => mwd39388fd_4f85_4d1c_b2a3_37857c595a2d; mwbfcf6773_1915_432c_b1d2_1f246094cc74, mw7cff9a0e_094d_498e_bf7f_7b162c61d63a, mwd39388fd_4f85_4d1c_b2a3_37857c595a2d mw10c97b8e_72aa_4f56_b3b9_c94baad7e213*mwbfcf6773_1915_432c_b1d2_1f246094cc74*mw7cff9a0e_094d_498e_bf7f_7b162c61d63a-mw0b6eb5f7_b133_4b3d_bf15_9fd6c2e9332d*mwd39388fd_4f85_4d1c_b2a3_37857c595a2d mw10c97b8e_72aa_4f56_b3b9_c94baad7e213=0.1; mw0b6eb5f7_b133_4b3d_bf15_9fd6c2e9332d=0.01
mwd39388fd_4f85_4d1c_b2a3_37857c595a2d + mwa54a9c38_c98b_45e5_8432_4119fb777e44 => mwd7bf31ba_b05c_4c45_bb2f_6a2468a2a507; mwd39388fd_4f85_4d1c_b2a3_37857c595a2d, mwa54a9c38_c98b_45e5_8432_4119fb777e44, mwd7bf31ba_b05c_4c45_bb2f_6a2468a2a507 mwe483687f_b591_4c42_9abc_7ea9f47470bf*mwd39388fd_4f85_4d1c_b2a3_37857c595a2d*mwa54a9c38_c98b_45e5_8432_4119fb777e44-mwcf964aba_9db6_46c5_b687_beafc5d89169*mwd7bf31ba_b05c_4c45_bb2f_6a2468a2a507 mwe483687f_b591_4c42_9abc_7ea9f47470bf=2.845; mwcf964aba_9db6_46c5_b687_beafc5d89169=0.96
mwd7bf31ba_b05c_4c45_bb2f_6a2468a2a507 => mwd39388fd_4f85_4d1c_b2a3_37857c595a2d + mw8f5a7b5c_ca4c_4a4c_85b1_e5d640c426bf; mwd7bf31ba_b05c_4c45_bb2f_6a2468a2a507 mwb881f20a_cf8a_493a_aa84_59ee90f26dd9*mwd7bf31ba_b05c_4c45_bb2f_6a2468a2a507 mwb881f20a_cf8a_493a_aa84_59ee90f26dd9=7.76
Curator's comment:
(added: 13 May 2013, 12:08:21, updated: 13 May 2013, 12:08:21)
The paper describes two models of EGFR signalling in normal (MODEL1304020000) and NSCLC (this model - MODEL1304020001) cells. Figure 4 of the reference publication is reproduced, where plot in red (NSCLC) can be obtained from this model (MODEL1304020001) and the plot in blue (normal cells) was obtained from MODEL1304020000. The model was simulated using COPASI v4.8 (Build 35). The plots were obtained using Gnuplot.