Kelsey Gasior

The Epithelial Mesenchymal Transition: A Multiscale Approach

We propose a mathematical and simulation-based model to examine the 
relationship between intracellular signaling pathways and the cellular 
behavior associated with the Epithelial-Mesenchymal Transition (EMT) in 
solid tumors –a crucial step in the metastasis of cancerous cells. EMT 
is a process by which epithelial cells undergo a phenotypic change and 
acquire invasive and migratory properties characteristic of the 
mesenchymal phenotype.  Several different signaling pathways can 
initiate this process, such as Wnt-Frizzled. Activation of this pathway 
stabilizes the beta-catenin protein, causing it to move to the nucleus 
and induce the expression of transcription factors such as Snail, Slug, 
and Twist.  These factors in turn suppress the expression of the 
E-cadherin protein, which sequesters beta-catenin to the cell surface 
and is essential for maintenance of cell-cell adhesion and the 
epithelial phenotype. After the EMT process is complete, the newly 
formed mesenchymal cells can break through the basal membrane into the 
blood stream and migrate to other locations in the body.  At these 
remote locations the cells can undergo a reverse process, the 
mesenchymal-epithelial transition (MET), which transforms them back into 
epithelial cells that form new secondary tumors.  We have developed an 
ordinary-differential-equation based model of the intracellular 
signaling pathways leading to EMT, which is then embedded into a 
multicellular spatial agent-based model to examine how these 
intracellular pathways contribute to the phenotypic and behavioral 
changes characteristic of EMT at the tissue level. This multi-scale 
modeling approach is ideally suited for comparison to experimental 
observations regarding EMT in solid tumors.

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Christian Haargaard Olsen

TBA