Skip to content

Mathematical Modeling Highlights the Complex Role of AKT in TRAIL-Induced Apoptosis of Colorectal Carcinoma Cells

Research output: Contribution to journalArticle

Standard

Mathematical Modeling Highlights the Complex Role of AKT in TRAIL-Induced Apoptosis of Colorectal Carcinoma Cells. / Anderson, Matthew W.; Moss, Joanna; Szalai, Robert; Lane, Jon.

In: iScience, Vol. 12, 22.02.2019, p. 182-193.

Research output: Contribution to journalArticle

Harvard

APA

Vancouver

Author

Bibtex

@article{6a91016d4e7e4998825d776c368063ee,
title = "Mathematical Modeling Highlights the Complex Role of AKT in TRAIL-Induced Apoptosis of Colorectal Carcinoma Cells",
abstract = "Protein kinase B/AKT is a highly connected protein involved in a range of signaling pathways. Although it is known to regulate several proteins in the apoptotic pathway, its system level effects remain poorly understood. We investigated the dynamic interactions between AKT and key apoptotic proteins, and constructed a deterministic Ordinary Differential Equation protein interaction model of extrinsic apoptosis. Incorporating AKT and its indirect inhibitor, PTEN, this was used to generate predictions of system dynamics. Using eigenanalysis, we identified AKT and cytochrome c as the protein species most sensitive to perturbations. Cell death assays in Type II HCT116 colorectal carcinoma cells revealed a tendency towards Type I cell death behavior in the XIAP-/- background, with cells displaying accelerated TRAIL-induced apoptosis. Finally, AKT inhibition experiments implicated AKT and not PTEN in influencing apoptotic proteins during early phases of TRAIL-induced apoptosis.",
keywords = "Cancer, Cell Biology, In Silico Biology",
author = "Anderson, {Matthew W.} and Joanna Moss and Robert Szalai and Jon Lane",
note = "Copyright {\circledC} 2019 The Author(s). Published by Elsevier Inc. All rights reserved.",
year = "2019",
month = "2",
day = "22",
doi = "10.1016/j.isci.2019.01.015",
language = "English",
volume = "12",
pages = "182--193",
journal = "iScience",
issn = "2589-0042",

}

RIS - suitable for import to EndNote

TY - JOUR

T1 - Mathematical Modeling Highlights the Complex Role of AKT in TRAIL-Induced Apoptosis of Colorectal Carcinoma Cells

AU - Anderson, Matthew W.

AU - Moss, Joanna

AU - Szalai, Robert

AU - Lane, Jon

N1 - Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.

PY - 2019/2/22

Y1 - 2019/2/22

N2 - Protein kinase B/AKT is a highly connected protein involved in a range of signaling pathways. Although it is known to regulate several proteins in the apoptotic pathway, its system level effects remain poorly understood. We investigated the dynamic interactions between AKT and key apoptotic proteins, and constructed a deterministic Ordinary Differential Equation protein interaction model of extrinsic apoptosis. Incorporating AKT and its indirect inhibitor, PTEN, this was used to generate predictions of system dynamics. Using eigenanalysis, we identified AKT and cytochrome c as the protein species most sensitive to perturbations. Cell death assays in Type II HCT116 colorectal carcinoma cells revealed a tendency towards Type I cell death behavior in the XIAP-/- background, with cells displaying accelerated TRAIL-induced apoptosis. Finally, AKT inhibition experiments implicated AKT and not PTEN in influencing apoptotic proteins during early phases of TRAIL-induced apoptosis.

AB - Protein kinase B/AKT is a highly connected protein involved in a range of signaling pathways. Although it is known to regulate several proteins in the apoptotic pathway, its system level effects remain poorly understood. We investigated the dynamic interactions between AKT and key apoptotic proteins, and constructed a deterministic Ordinary Differential Equation protein interaction model of extrinsic apoptosis. Incorporating AKT and its indirect inhibitor, PTEN, this was used to generate predictions of system dynamics. Using eigenanalysis, we identified AKT and cytochrome c as the protein species most sensitive to perturbations. Cell death assays in Type II HCT116 colorectal carcinoma cells revealed a tendency towards Type I cell death behavior in the XIAP-/- background, with cells displaying accelerated TRAIL-induced apoptosis. Finally, AKT inhibition experiments implicated AKT and not PTEN in influencing apoptotic proteins during early phases of TRAIL-induced apoptosis.

KW - Cancer

KW - Cell Biology

KW - In Silico Biology

UR - http://www.scopus.com/inward/record.url?scp=85065772264&partnerID=8YFLogxK

U2 - 10.1016/j.isci.2019.01.015

DO - 10.1016/j.isci.2019.01.015

M3 - Article

C2 - 30690394

AN - SCOPUS:85065772264

VL - 12

SP - 182

EP - 193

JO - iScience

JF - iScience

SN - 2589-0042

ER -