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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{dagger}

Tsuyoshi Kobayashi,1,2 Shin-ichiro Hino,1 Naohide Oue,3 Toshimasa Asahara,2 Massimo Zollo,4 Wataru Yasui,3 and Akira Kikuchi1*

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.


* Corresponding author. Mailing address: Department of Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8551, Japan. Phone: 81-82-257-5130. Fax: 81-82-257-5134. E-mail: akikuchi{at}hiroshima-u.ac.jp.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.


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.




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