Rottlerin inhibits migration of follicular thyroid carcinoma cells by PKCdelta-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 microM) 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 beta1, 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 PKCdelta activity since siRNA knockdown of PKCdelta did not recapitulate the effects of rottlerin on cell adhesion and migration. Furthermore, activation of PKCdelta 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 PKCdelta-independent manner, and might play as a mitochondrial uncoupler role in these events.
Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan.
Chien-Jung
CJ
Lin
Chieh-Yu
CY
Lin
Ying
Y
Chen
Shih-Horng
SH
Huang
Seu-Mei
SM
Wang
D000098:Acetophenones / Q000494:pharmacology*; D017209:Apoptosis; D001578:Benzopyrans / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D005434:Flow Cytometry; D022001:Focal Adhesions; D006801:Humans; D008856:Microscopy, Fluorescence; D051745:Protein Kinase C-delta / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering; D013964:Thyroid Neoplasms / Q000201:enzymology / Q000473:pathology*
D000098:Acetophenones; D001578:Benzopyrans; D034741:RNA, Small Interfering; C085746:rottlerin; D051745:Protein Kinase C-delta