Cancer cell invasion is a critical phenomenon in cancer pathogenesis. Glycogen synthase kinase-3 beta (GSK-3 beta) has been reported to regulate cancer cell invasion both negatively and positively. Thus, the net effect of GSK-3 beta on invasion is unclear. In this report, we showed that GSK-3 beta inhibitors induced dysregulation of the actin cytoskeleton and functional insufficiency of focal adhesion, which resulted in suppressed invasion. In addition, WAVE2, an essential molecule for actin fibre branching, was down-regulated after GSK-3 beta inhibition. Collectively, we propose that the WAVE2-actin cytoskeleton axis is an important target of GSK-3 beta inhibitors in cancer cell invasion. (C) 2015 Elsevier Inc. All rights reserved.