Activation of the non-canonical Dvl-Rac1-JNK pathway by Frizzled homologue 10 in human synovial sarcoma.
We previously reported that Frizzled homologue 10 (FZD10), a member of the Wnt signal receptor family, was highly and specifically upregulated in synovial sarcoma and played critical roles in its cell survival and growth. We here report a possible molecular mechanism of the FZD10 signaling in synovial sarcoma cells. We found a significant enhancement of phosphorylation of the Dishevelled (Dvl)2/Dvl3 complex as well as activation of the Rac1-JNK cascade in synovial sarcoma cells in which FZD10 was overexpressed. Activation of the FZD10-Dvls-Rac1 pathway induced lamellipodia formation and enhanced anchorage-independent cell growth cells. FZD10 overexpression also caused the destruction of the actin cytoskeleton structure, probably through the downregulation of the RhoA activity. Our results have strongly implied that FZD10 transactivation causes the activation of the non-canonical Dvl-Rac1-JNK pathway and plays critical roles in the development/progression of synovial sarcomas.
Fukukawa
C
C
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Nagayama
S
S
Tsunoda
T
T
Toguchida
J
J
Nakamura
Y
Y
Katagiri
T
T
D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002448:Cell Adhesion / Q000502:physiology; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003599:Cytoskeleton / Q000378:metabolism; D000072261:Dishevelled Proteins; D004789:Enzyme Activation; D051157:Frizzled Receptors / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D047468:Immunoprecipitation; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011554:Pseudopodia / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013584:Sarcoma, Synovial / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D015533:Transcriptional Activation; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism
D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C000606581:DVL2 protein, human; C000606584:DVL3 protein, human; D000072261:Dishevelled Proteins; C121168:FZD10 protein, human; D051157:Frizzled Receptors; D010750:Phosphoproteins; C107953:RAC1 protein, human; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D048031:JNK Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein