Rottlerin Inhibits Migration Of Follicular Thyroid Carcinoma Cells By Pkc Delta-Independent Destabilization Of The Focal Adhesion Complex

This study examined the effect of rottlerin on the focal adhesion-mediated cell migration of CGTH W-2 human follicular thyroid carcinoma cells. Rottlerin (10 mu M) resulted in decreased adhesion of CGTH W-2 cells to matrix substance, which was correlated with metastatic potential. Rottlerin treatment also resulted in a marked reduction in the migration of CGTH W-2 cells. Protein levels of integrin beta 1, FAK, and paxillin were decreased by rottlerin. Consistent with this, immunostaining of FAK, vinculin, and paxillin revealed disassembly of the focal adhesions. Disruption of actin stress fibers was noted, which was compatible with reduced expression levels and activities of Rac-1 and Rho. The effect of rottlerin on cell migration was not attributable to inhibition of PKC delta activity since siRNA knockdown of PKC delta did not recapitulate the effects of rottlerin on cell adhesion and migration. Furthermore, activation of PKC delta by phorbol esters failed to restore the rottlerin-inhibited migratory ability. The mitochondrial uncoupler, carbonylcyanide-4-(trifluoromethoxy)-phenylhydrazone, was able to mimic several rottlerin's effects. In summary, we demonstrated that rottlerin inhibits the migration of CGTH W-2 cells by disassembly of focal adhesion complexes in a PKC delta-independent manner, and might play as a mitochondrial uncoupler role in these events. J. Cell. Biochem. 110: 428-437, 2010. (C) 2010 Wiley-Liss, Inc.