Received for publication July 18, 2006.
Revised November 7, 2006.
Accepted for publication November 7, 2006.

Microtubule Destabilizing Agents Induce Focal Adhesion Structures Disorganization and Anoikis in Cancer Cells

Abstract

Microtubule disruption provokes cytoskeleton and cell adhesion changes whose importance for apoptosis induction remains unclear. The present study focuses on the functional and the molecular adhesion kinetics that is induced by microtubule disruption-mediated apoptosis. We showed that antimicrotubules induce a biphasic sequence of adhesion response that precedes the onset of apoptosis and Focal Adhesion Kinase hydrolysis. Anti-microtubule first induced an increase of the cellular adhesion paralleled by the raise of focal adhesion sites and actin contractility, which is followed by a sharp decrease of cell adhesion, disorganization of focal adhesion and actin stress fibers. The latter sequence of events ends by cell rounding, detachment from the extracellular matrix and cell death. microtubule-disrupting agents induced a sustained paxillin phosphorylation, before the activation of apoptosis, which requires the prior activation of ERK and p38 but not JNK. Interestingly, ILK overexpression rescued the anti-microtubule-mediated loss of cell viability. Altogether, these results propound that anti-microtubule agents induce anoikis through the loss of focal adhesion structures integrity.

Key words: Adhesion, Anoikis, Antimicrotubule agents, Chloroethylureas, Focal adhesion structture, Paxillin phosphorylation