Gleevec, an Abl family inhibitor, produces a profound change in cell shape and migration.

TitleGleevec, an Abl family inhibitor, produces a profound change in cell shape and migration.
Publication TypeJournal Article
Year of Publication2013
AuthorsZ Chen, E Lessey, ME Berginski, L Cao, J Li, X Trepat, M Itano, SM Gomez, M Kapustina, C Huang, K Burridge, G Truskey, and K Jacobson
JournalPloS one
Volume8
Issue1
Start Pagee52233
Date Published01/2013
Abstract

The issue of how contractility and adhesion are related to cell shape and migration pattern remains largely unresolved. In this paper we report that Gleevec (Imatinib), an Abl family kinase inhibitor, produces a profound change in the shape and migration of rat bladder tumor cells (NBTII) plated on collagen-coated substrates. Cells treated with Gleevec adopt a highly spread D-shape and migrate more rapidly with greater persistence. Accompanying this more spread state is an increase in integrin-mediated adhesion coupled with increases in the size and number of discrete adhesions. In addition, both total internal reflection fluorescence microscopy (TIRFM) and interference reflection microscopy (IRM) revealed a band of small punctate adhesions with rapid turnover near the cell leading margin. These changes led to an increase in global cell-substrate adhesion strength, as assessed by laminar flow experiments. Gleevec-treated cells have greater RhoA activity which, via myosin activation, led to an increase in the magnitude of total traction force applied to the substrate. These chemical and physical alterations upon Gleevec treatment produce the dramatic change in morphology and migration that is observed.

DOI10.1371/journal.pone.0052233
Short TitlePloS one