title: Modeling the influence of the E-cadherin-beta-catenin pathway in cancer cell invasion: a multiscale approach.
abstract: In this article, we show, using a mathematical multiscale model, how cell adhesion may be regulated by interactions between E-cadherin and beta-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. beta-catenin is an intracellular protein associated with the actin cytoskeleton of a cell. E-cadherins bind to beta-catenin to form a complex which can interact both with neighboring cells to form bonds, and with the cytoskeleton of the cell. When cells detach from one another, beta-catenin is released into the cytoplasm, targeted for degradation, and downregulated. In this process there are multiple protein-complexes involved which interact with beta-catenin and E-cadherin. Within a mathematical individual-based multiscale 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.
authors.affiliation: French National Institute for Research in Computer Science and Control (INRIA), Domaine de Voluceau-Rocquencourt, Le Chesnay, France. ignacio.ramis_conde@inria.fr
authors.forename: Ignacio
authors.initials: I
authors.lastname: Ramis-Conde
authors.forename: Dirk
authors.initials: D
authors.lastname: Drasdo
authors.forename: Alexander R A
authors.initials: AR
authors.lastname: Anderson
authors.forename: Mark A J
authors.initials: MA
authors.lastname: Chaplain
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D002448:Cell Adhesion; D003198:Computer Simulation; D006801:Humans; D008954:Models, Biological; D009361:Neoplasm Invasiveness / Q000473:pathology* / Q000503:physiopathology*; D009369:Neoplasms / Q000473:pathology* / Q000503:physiopathology*; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D015820:Cadherins; D051176:beta Catenin