title: Gleevec, an Abl family inhibitor, produces a profound change in cell shape and migration.
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.
authors.affiliation: Department of Cell Biology and Physiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina, United States of America.
authors.forename: Zaozao
authors.initials: Z
authors.lastname: Chen
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Lessey
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Berginski
authors.forename: Li
authors.initials: L
authors.lastname: Cao
authors.forename: Jonathan
authors.initials: J
authors.lastname: Li
authors.forename: Xavier
authors.initials: X
authors.lastname: Trepat
authors.forename: Michelle
authors.initials: M
authors.lastname: Itano
authors.forename: Shawn M
authors.initials: SM
authors.lastname: Gomez
authors.forename: Maryna
authors.initials: M
authors.lastname: Kapustina
authors.forename: Cai
authors.initials: C
authors.lastname: Huang
authors.forename: Keith
authors.initials: K
authors.lastname: Burridge
authors.forename: George
authors.initials: G
authors.lastname: Truskey
authors.forename: Ken
authors.initials: K
authors.lastname: Jacobson
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects*; D048430:Cell Shape / Q000187:drug effects*; D000068877:Imatinib Mesylate; D008857:Microscopy, Interference; D009218:Myosins / Q000378:metabolism; D010641:Phenotype; D010879:Piperazines / Q000494:pharmacology*; D016315:Proto-Oncogene Proteins c-abl / Q000037:antagonists & inhibitors / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D033081:Shear Strength; D013314:Stress, Mechanical; D014407:Tumor Cells, Cultured; D001743:Urinary Bladder / Q000187:drug effects; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy*; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D000199:Actins; D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D000068877:Imatinib Mesylate; D016315:Proto-Oncogene Proteins c-abl; D009218:Myosins; D020742:rhoA GTP-Binding Protein