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Activation of the non-canonical Dvl–Rac1–JNK pathway by Frizzled homologue 10 in human synovial sarcoma

Oncogene volume 28, pages 1110–1120 (2009)Cite this article

Abstract

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.

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Acknowledgements

We thank Dr Ryo Takata for statistical analysis, and Ms Kie Naito, Ms Yoshiko Fujisawa, Ms Akiko Konuma, Ms Aya Sasaki and Ms Kyoko Kijima for excellent technical assistance.

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Author notes

  1. T Katagiri

    Present address: 4Current address: Division of Genome Medicine, Institute for Genome Research, The University of Tokushima, Tokushima 770-8503, Japan,

Authors and Affiliations

  1. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    C Fukukawa, S Nagayama, Y Nakamura & T Katagiri

  2. Laboratory for Medical Informatics, SNP Research Center, RIKEN (Institute of Physical and Chemical Research), Yokohama, Japan

    T Tsunoda

  3. Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan

    J Toguchida

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  1. C Fukukawa
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Correspondence to T Katagiri.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc)

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Fukukawa, C., Nagayama, S., Tsunoda, T. et al. Activation of the non-canonical Dvl–Rac1–JNK pathway by Frizzled homologue 10 in human synovial sarcoma. Oncogene 28, 1110–1120 (2009). https://doi.org/10.1038/onc.2008.467

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