Modeling HIF-ILK Interaction Using Continuous Petri Nets
Journal:
arXiv
Published Date:
Mar 10, 2025
Abstract
Oxygen concentration in tumor micro-environment is a well-established signal
that can induce aggressive cancer behaviour. In particular, low oxygen levels
(hypoxia) activate the Hypoxia-Inducible Factor(HIF) pathway which has an array
of target systems. One of these systems is Integrin-Linked Kinase (ILK)
pathway, which influences key signaling pathways for cell survival,
proliferation, and migration. Hence, this paper aimed to explore the
interconnection between these two pathways. Using the Petri net modeling tool
Snoopy, an established HIF network model was transformed to be a continuous
Petri net. Subsequently, the network was expanded to incorporate a feedback
element from the ILK pathway to HIF, based on gene expression data. The
resulting model conserved the oxygen switch response of the original HIF model
and positively amplified HIF's output. Therefore, this model provides a
starting point for establishing a system reflecting crucial effect on
hypoxia-induced cancer behavior, and could potentially serve as a basis for
future drug development.
