Modelling the influence of the E-Cadherin - -Catenin pathway in cancer cell invasion: A multi-scale approach

¹ University of Dundee
² French National Institute for Research in Computer Science and Control (INRIA)

^* To whom correspondence should be addressed. E-mail: dirk.drasdo{at}inria.fr.

Submitted on June 11, 2007
Revised on July 9, 2007
Accepted on 3 January 2008

	Abstract

In this paper, we show using a mathematical multi-scale model, how cell adhesion may be regulated by interactions between E-cadherin and -catenin and how the control of cell adhesion may be related to cell migration, to the epithelial-mesenchymal transition and to invasion in populations of eukaryotic cells. E-cadherin mediates cell-cell adhesion and plays a critical role in the formation and maintenance of junctional contacts between cells. Loss of E-cadherin mediated adhesion is a key feature of the epithelial-mesenchymal transition. -catenin is an intracellular protein associated with the actin cytoskeleton of a cell. E-cadherins bind to -catenin to form a complex which can interact both with neighbouring cells to form bonds, and with the cytoskeleton of the cell. When cells detach from one another, -catenin is released into the cytoplasm, targeted for degradation and down-regulated. In this process there are multiple protein-complexes involved which interact with -catenin and E-cadherin. Within a mathematical individual-based multi-scale model we are able to explain experimentally observed patterns solely by a variation of cell-cell adhesive interactions. Implications for cell migration and cancer invasion are also discussed.

Key Words: Cancer Invasion, Cell-adhesion, Multi-scale modelling, \beta-catenin, agent-based model, single-cell-based-model