Collections > Electronic Theses and Dissertations > Inhibition of Abl family kinases produces a profound change in cell shape and migration

Cell migration is fundamental to establishing and maintaining the proper organization of multi-cellular organisms. In this dissertation we reviewed and discussed the biological process of single cell migration in two-dimensional and three-dimensional environments. We reported that Gleevec (Imatinib), an Abl family kinase inhibitor, produces a profound change in the shape and migration of rat bladder tumor cells (NBT-II) plated on collagen-coated substrates. Cells treated with Gleevec adopt a highly spread D-shape (similar to fish keratocytes) and migrate more rapidly with greater persistence. Our finding indicate integrin mediated adhesion changes happened with the inhibition of Abl-family kinases, while RhoA activity increased in this cases, which via myosin activation, led to an increase in the magnitude of total traction force applied to the substrate. We also discovered a special band of small punctate, rapidly turning over adhesions near the leading margin of spread D-shape NBT-I