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

ABSTRACT 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.

[1]  A. Mercurio,et al.  Hypoxia stimulates carcinoma invasion by stabilizing microtubules and promoting the Rab11 trafficking of the alpha6beta4 integrin. , 2005, Cancer research.

[2]  K. Kaibuchi,et al.  GSK-3β Regulates Phosphorylation of CRMP-2 and Neuronal Polarity , 2005, Cell.

[3]  Anna Huttenlocher,et al.  Calpain-mediated proteolysis of talin regulates adhesion dynamics , 2004, Nature Cell Biology.

[4]  S. Vijayaraghavan,et al.  Changes in sperm glycogen synthase kinase-3 serine phosphorylation and activity accompany motility initiation and stimulation. , 2004, Journal of andrology.

[5]  Patricia J Keely,et al.  Focal adhesion regulation of cell behavior. , 2004, Biochimica et biophysica acta.

[6]  L. Aravind,et al.  Prune cAMP phosphodiesterase binds nm23-H1 and promotes cancer metastasis. , 2004, Cancer cell.

[7]  R. Jope,et al.  The glamour and gloom of glycogen synthase kinase-3. , 2004, Trends in biochemical sciences.

[8]  T. Dale,et al.  Protein Kinase B/Akt Acts via Glycogen Synthase Kinase 3 To Regulate Recycling of αvβ3 and α5β1 Integrins , 2004, Molecular and Cellular Biology.

[9]  Donna J. Webb,et al.  FAK–Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly , 2004, Nature Cell Biology.

[10]  G. Borisy,et al.  Cell Migration: Integrating Signals from Front to Back , 2003, Science.

[11]  H. Larjava,et al.  Glycogen synthase kinase-3 regulates formation of long lamellipodia in human keratinocytes , 2003, Journal of Cell Science.

[12]  Yoshiharu Matsuura,et al.  Sumoylation is involved in β‐catenin‐dependent activation of Tcf‐4 , 2003 .

[13]  N. Cordes,et al.  Cell adhesion to the extracellular matrix protein fibronectin modulates radiation-dependent G2 phase arrest involving integrin-linked kinase (ILK) and glycogen synthase kinase-3β (GSK-3β) in vitro , 2003, British Journal of Cancer.

[14]  T. Michiue,et al.  Casein Kinase Iε Enhances the Binding of Dvl-1 to Frat-1 and Is Essential for Wnt-3a-induced Accumulation of β-Catenin* , 2003, The Journal of Biological Chemistry.

[15]  J. Parsons,et al.  Focal adhesion kinase: the first ten years , 2003, Journal of Cell Science.

[16]  B. Doble,et al.  GSK-3: tricks of the trade for a multi-tasking kinase , 2003, Journal of Cell Science.

[17]  A. Hall,et al.  Cdc42 regulates GSK-3β and adenomatous polyposis coli to control cell polarity , 2003, Nature.

[18]  Irina Kaverina,et al.  Microtubules meet substrate adhesions to arrange cell polarity. , 2003, Current opinion in cell biology.

[19]  P. Steeg,et al.  Basic and Translational Advances in Cancer Metastasis: Nm23 , 2003, Journal of bioenergetics and biomembranes.

[20]  T. Dale,et al.  The Regulation of Glycogen Synthase Kinase-3 Nuclear Export by Frat/GBP* , 2002, The Journal of Biological Chemistry.

[21]  Akira Kikuchi,et al.  Interaction of POB1, a Downstream Molecule of Small G Protein Ral, with PAG2, a Paxillin-binding Protein, Is Involved in Cell Migration* , 2002, The Journal of Biological Chemistry.

[22]  N. Yorioka,et al.  A-Kinase Anchoring Protein AKAP220 Binds to Glycogen Synthase Kinase-3β (GSK-3β) and Mediates Protein Kinase A-dependent Inhibition of GSK-3β* , 2002, The Journal of Biological Chemistry.

[23]  P. Keely,et al.  Characterization of an activated mutant of focal adhesion kinase: 'SuperFAK'. , 2002, The Biochemical journal.

[24]  Ling Song,et al.  Direct, activating interaction between glycogen synthase kinase-3β and p53 after DNA damage , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[25]  B. Eickholt,et al.  An inactive pool of GSK-3 at the leading edge of growth cones is implicated in Semaphorin 3A signaling , 2002, The Journal of cell biology.

[26]  Donna J. Webb,et al.  Adhesion assembly, disassembly and turnover in migrating cells – over and over and over again , 2002, Nature Cell Biology.

[27]  J. Heino,et al.  Integrin α2β1 Promotes Activation of Protein Phosphatase 2A and Dephosphorylation of Akt and Glycogen Synthase Kinase 3β , 2002, Molecular and Cellular Biology.

[28]  R. Jope,et al.  The multifaceted roles of glycogen synthase kinase 3β in cellular signaling , 2001, Progress in Neurobiology.

[29]  A. Reymond,et al.  Amplification and overexpression of PRUNE in human sarcomas and breast carcinomas–a possible mechanism for altering the nm23-H1 activity , 2001, Oncogene.

[30]  P. Cohen,et al.  The renaissance of GSK3 , 2001, Nature Reviews Molecular Cell Biology.

[31]  H. Koh,et al.  Akt/PKB promotes cancer cell invasion via increased motility and metalloproteinase production. , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[32]  A. Huttenlocher,et al.  Integrin-mediated adhesion regulates cell polarity and membrane protrusion through the Rho family of GTPases. , 2001, Molecular biology of the cell.

[33]  L. Ellis,et al.  Induction of angiogenesis by hyperplastic colonic mucosa adjacent to colon cancer. , 2000, The American journal of pathology.

[34]  C. W. Scott,et al.  Regulation and localization of tyrosine216 phosphorylation of glycogen synthase kinase-3beta in cellular and animal models of neuronal degeneration. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[35]  T. Andoh,et al.  Yeast Glycogen Synthase Kinase 3 Is Involved in Protein Degradation in Cooperation with Bul1, Bul2, and Rsp5 , 2000, Molecular and Cellular Biology.

[36]  A. Kikuchi,et al.  Roles of Axin in the Wnt signalling pathway. , 1999, Cellular signalling.

[37]  Akira Kikuchi,et al.  DIX Domains of Dvl and Axin Are Necessary for Protein Interactions and Their Ability To Regulate β-Catenin Stability , 1999, Molecular and Cellular Biology.

[38]  R. Jope,et al.  Insulin Transiently Increases Tau Phosphorylation , 1999, Journal of neurochemistry.

[39]  D. Carter.  TNM Classification of Malignant Tumors , 1998 .

[40]  Akira Kikuchi,et al.  Axil, a Member of the Axin Family, Interacts with Both Glycogen Synthase Kinase 3β and β-Catenin and Inhibits Axis Formation ofXenopus Embryos , 1998, Molecular and Cellular Biology.

[41]  Richard A. Szucs,et al.  TNM Classification of Malignant Tumors. 5th ed , 1998 .

[42]  Akira Kikuchi,et al.  Axin, a negative regulator of the Wnt signaling pathway, forms a complex with GSK‐3β and β‐catenin and promotes GSK‐3β‐dependent phosphorylation of β‐catenin , 1998 .

[43]  James R. Woodgett,et al.  Lithium inhibits glycogen synthase kinase-3 activity and mimics Wingless signalling in intact cells , 1996, Current Biology.

[44]  A. Huttenlocher,et al.  Modulation of cell migration by integrin-mediated cytoskeletal linkages and ligand-binding affinity , 1996, Journal of Cell Biology.

[45]  D. Melton,et al.  A molecular mechanism for the effect of lithium on development. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[46]  S. Aizawa,et al.  Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK-deficient mice , 1995, Nature.

[47]  J. Parsons,et al.  Autophosphorylation of the focal adhesion kinase, pp125FAK, directs SH2-dependent binding of pp60src , 1994, Molecular and cellular biology.

[48]  J. Woodgett,et al.  Glycogen synthase kinase-3: functions in oncogenesis and development. , 1992, Biochimica et biophysica acta.

[49]  J. Willson,et al.  Induction of nm23 gene expression in human colonic neoplasms and equal expression in colon tumors of high and low metastatic potential. , 1991, Journal of the National Cancer Institute.

[50]  J. Woodgett,et al.  Molecular cloning and expression of glycogen synthase kinase‐3/factor A. , 1990, The EMBO journal.

[51]  J. Biggs,et al.  Analysis of the lethal interaction between the prune and Killer of prune mutations of Drosophila. , 1988, Genes & development.

[52]  A. Cossu,et al.  Overexpression of h-prune in breast cancer is correlated with advanced disease status. , 2005, Clinical cancer research : an official journal of the American Association for Cancer Research.

[53]  吉村 武.  GSK-3β regulates phosphorylation of CRMP-2 and neuronal polarity , 2005 .

[54]  Akira Kikuchi,et al.  Yeast glycogen synthase kinase-3 activates Msn2p-dependent transcription of stress responsive genes. , 2003, Molecular biology of the cell.

[55]  G. Bokoch,et al.  Assay of Cdc42, Rac, and Rho GTPase activation by affinity methods. , 2002, Methods in enzymology.

[56]  山本 英樹.  Axil, a member of the Axin family, interacts with both glycogen synthase kinase 3β and β-catenin and inhibits Axis formation of Xenopus embryos , 2001 .

[57]  R. Nusse,et al.  Mechanisms of Wnt signaling in development. , 1998, Annual review of cell and developmental biology.

[58]  G. Brooker,et al.  Assay of cyclic nucleotide phosphodiesterases with radioactive substrates. , 1974, Methods in enzymology.