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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Chen, Z; Lessey, E; Berginski, ME; Cao, L; Li, J; Trepat, X; Itano, M; Gomez, SM; Kapustina, M; Huang, C; Burridge, K; Truskey, G; Jacobson, K

Published Date

  • January 2, 2013

Published In

Volume / Issue

  • 8 / 1

Start / End Page

  • e52233 -

PubMed ID

  • 23300967

Pubmed Central ID

  • 23300967

Electronic International Standard Serial Number (EISSN)

  • 1932-6203

International Standard Serial Number (ISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0052233

Language

  • eng