Authors:
Jaroslaw Smieja
1
;
Malgorzata Kardynska
1
;
Anna Naumowicz
1
;
Patryk Janus
2
;
Piotr Widlak
3
and
Marek Kimmel
4
Affiliations:
1
Silesian University of Technology, Poland
;
2
Silesian University of Technology and Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Poland
;
3
Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Poland
;
4
Silesian University of Technology and Rice University, Poland
Keyword(s):
Signalling Pathways, NFkB, HSF, HSP, Heat Shock.
Related
Ontology
Subjects/Areas/Topics:
Agents
;
Artificial Intelligence
;
Bioinformatics
;
Biomedical Engineering
;
Enterprise Information Systems
;
Information Systems Analysis and Specification
;
Methodologies and Technologies
;
Model Design and Evaluation
;
Operational Research
;
Simulation
;
Systems Biology
Abstract:
Motivation: Inhibition of NFkB pathway is known to promote apoptosis and therefore may constitute one of the goals in anticancer therapies. Experimental results show that heat shock induces such inhibition in cancer cells. However, the mechanisms of interactions between heat shock and NFkB pathways are not fully understood yet. Development of a combined mathematical model of these pathways and its subsequent computational analysis should help to uncover these mechanisms and determine the time window in which heat shock treatment preceding chemotherapy would be the most efficient.
Results: An original mathematical model has been developed, allowing for computational testing of various hypotheses concerning main sources of interplay between HSF and NFkB pathways. Computational analysis strongly suggests that the competition for IKK, known from literature, cannot be the only mechanism. Two plausible hypotheses are that either a kinase activating IKK can misfold due to heat shock or tha
t heat shock affects TNF receptors, blocking activation of NFkB pathway at the cell membrane.
(More)