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Molecular and Cellular Biology, February 2006, p. 898-911, Vol. 26, No. 3
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.3.898-911.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Glycogen Synthase Kinase 3 and h-prune Regulate Cell Migration by Modulating Focal Adhesions

Departments of Biochemistry,¹ Surgery,² Molecular Pathology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan,³ CEINGE, Biotecnologie Avanzate s.c.ar.l., Napoli, Italy⁴

Received 25 July 2005/ Returned for modification 2 September 2005/ Accepted 4 November 2005

h-prune, which has been suggested to be involved in cell migration, was identified as a glycogen synthase kinase 3 (GSK-3)-binding protein. Treatment of cultured cells with GSK-3 inhibitors or small interfering RNA (siRNA) for GSK-3 and h-prune inhibited their motility. The kinase activity of GSK-3 was required for the interaction of GSK-3 with h-prune. h-prune was localized to focal adhesions, and the siRNA for GSK-3 or h-prune delayed the disassembly of paxillin. The tyrosine phosphorylation of focal adhesion kinase (FAK) and the activation of Rac were suppressed in GSK-3 or h-prune knocked-down cells. GSK-3 inhibitors suppressed the disassembly of paxillin and the activation of FAK and Rac. Furthermore, h-prune was highly expressed in colorectal and pancreatic cancers, and the positivity of the h-prune expression was correlated with tumor invasion. These results suggest that GSK-3 and h-prune cooperatively regulate the disassembly of focal adhesions to promote cell migration and that h-prune is useful as a marker for tumor aggressiveness.

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