Complex Systems Biology Approach in Connecting PI3K-Akt and NF-κB Pathways in Prostate Cancer.
Cell Line, Tumor
Cell Proliferation
/ drug effects
Computer Simulation
Epidermal Growth Factor
/ pharmacology
Humans
I-kappa B Kinase
/ metabolism
I-kappa B Proteins
/ metabolism
Male
NF-kappa B
/ metabolism
Phosphatidylinositol 3-Kinases
/ metabolism
Phosphorylation
/ drug effects
Prostatic Neoplasms
/ metabolism
Proto-Oncogene Proteins c-akt
/ metabolism
Signal Transduction
/ drug effects
Systems Biology
Transcription, Genetic
/ drug effects
NF-κB
PI3K/Akt
systems biology
Journal
Cells
ISSN: 2073-4409
Titre abrégé: Cells
Pays: Switzerland
ID NLM: 101600052
Informations de publication
Date de publication:
26 02 2019
26 02 2019
Historique:
received:
03
01
2019
revised:
05
02
2019
accepted:
24
02
2019
entrez:
1
3
2019
pubmed:
1
3
2019
medline:
1
3
2019
Statut:
epublish
Résumé
Phosphatidylinositol 3'-OH kinase (PI3K)-Akt and transcription factor NF-κB are important molecules involved in the regulation of cell proliferation, apoptosis, and oncogenesis. Both PI3K-Akt and Nuclear Factor-kappaB (NF-κB) are involved in the development and progression of prostate cancer, however, the crosstalk and molecules connecting these pathway remains unclear. A multilevel system representation of the PI3K-Akt and NF-κB pathways was constructed to determine which signaling components contribute to adaptive behavior and coordination. In silico experiments conducted using PI3K-Akt and NF-κB, mathematical models were modularized using biological functionality and were validated using a cell culture system. Our analysis demonstrates that a component representing the IκB kinase (IKK) complex can coordinate these two pathways. It is expected that interruption of this molecule could represent a potential therapeutic target for prostate cancer.
Identifiants
pubmed: 30813597
pii: cells8030201
doi: 10.3390/cells8030201
pmc: PMC6468646
pii:
doi:
Substances chimiques
I-kappa B Proteins
0
NF-kappa B
0
Epidermal Growth Factor
62229-50-9
Phosphatidylinositol 3-Kinases
EC 2.7.1.-
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
I-kappa B Kinase
EC 2.7.11.10
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Références
Nat Rev Clin Oncol. 2014 Mar;11(3):167-76
pubmed: 24492837
Curr Cancer Drug Targets. 2010 Mar;10(2):135-46
pubmed: 20088800
Int J Cancer. 2007 Oct 1;121(7):1424-32
pubmed: 17551921
CA Cancer J Clin. 2018 Jan;68(1):7-30
pubmed: 29313949
Nat Rev Cancer. 2012 Jan 19;12(2):121-32
pubmed: 22257950
Mol Cell Biol. 2002 Apr;22(8):2862-70
pubmed: 11909978
Neoplasia. 2004 Jul-Aug;6(4):390-400
pubmed: 15256061
Cancer. 2009 Jul 1;115(13 Suppl):3078-84
pubmed: 19544549
Prostate. 2002 Aug 1;52(3):183-200
pubmed: 12111695
FEBS Lett. 2006 Feb 6;580(3):822-30
pubmed: 16413545
J Biol Chem. 2002 Feb 8;277(6):3863-9
pubmed: 11733537
J Interferon Cytokine Res. 2012 Apr;32(4):152-8
pubmed: 22149351
Oncogene. 2008 Sep 18;27(41):5443-53
pubmed: 18794879
Int J Oncol. 2014 Nov;45(5):1793-801
pubmed: 25120209
Mol Syst Biol. 2017 Jan 24;13(1):904
pubmed: 28123004
Int J Cancer. 2009 Dec 15;125(12):2863-70
pubmed: 19609947
Cell Death Differ. 2006 May;13(5):738-47
pubmed: 16485028
Arch Esp Urol. 2014 Jun;67(5):383-7
pubmed: 24914836
Int J Mol Sci. 2015 Sep 03;16(9):21138-52
pubmed: 26404259
Biochem J. 2003 Jul 15;373(Pt 2):451-63
pubmed: 12691603
Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12962-7
pubmed: 19470463
Biomed Res Int. 2015;2015:674039
pubmed: 26788504
PLoS Comput Biol. 2016 Apr 14;12(4):e1004820
pubmed: 27078000
Science. 2005 Sep 16;309(5742):1857-61
pubmed: 16166517
J Immunol. 2003 Jun 1;170(11):5630-5
pubmed: 12759443
Front Biosci (Landmark Ed). 2016 Jun 01;21:1084-91
pubmed: 27100493
Carcinogenesis. 1997 Jun;18(6):1215-23
pubmed: 9214605
Eur J Cancer. 2013 Jul;49(10):2441-8
pubmed: 23541563
Genes (Basel). 2018 Jan 09;9(1):
pubmed: 29315242
Nat Rev Urol. 2018 Oct;15(10):627-642
pubmed: 30065357
Curr Opin Cell Biol. 2017 Apr;45:62-71
pubmed: 28343126
Ann Med. 2014 Sep;46(6):372-83
pubmed: 24897931
Nature. 1999 Sep 2;401(6748):82-5
pubmed: 10485710
Front Oncol. 2013 Sep 17;3:240
pubmed: 24062990
Biochim Biophys Acta. 2011 Nov;1813(11):1938-45
pubmed: 21708191
J Biol Chem. 1999 Oct 15;274(42):30169-81
pubmed: 10514507
BJU Int. 2014 Aug;114(2):168-76
pubmed: 24215139
Sci STKE. 2006 Oct 17;2006(357):re13
pubmed: 17047224
CA Cancer J Clin. 2018 Nov;68(6):394-424
pubmed: 30207593
Mol Cell Biol. 1999 Jul;19(7):4798-805
pubmed: 10373529
J Cell Sci. 2002 Jan 1;115(Pt 1):141-51
pubmed: 11801732
BJU Int. 2003 Mar;91(4):417-20
pubmed: 12603426
Nat Rev Mol Cell Biol. 2018 Sep;19(9):547-562
pubmed: 29858604
Prostate. 2005 Aug 1;64(3):224-39
pubmed: 15712212
Cancer Treat Rev. 2004 Apr;30(2):193-204
pubmed: 15023437