Activation of the non-canonical Dvl-Rac1-JNK pathway by Frizzled homologue 10 in human synovial sarcoma
Activation of the non-canonical Dvl-Rac1-JNK pathway by Frizzled homologue 10 in human synovial sarcoma
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DOI：
10.1038/onc.2008.467
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发表时间：
2009-02-01
期刊：
影响因子：
8
通讯作者：
Katagiri, T.
中科院分区：
文献类型：
--
作者：
Fukukawa, C.;Nagayama, S.;Katagiri, T.
FZD10是Wnt信号受体家族的一员，在滑膜肉瘤中表达上调，在滑膜肉瘤的生存和生长过程中发挥重要作用。我们在这里报道了FZD10信号在滑膜肉瘤细胞中的一个可能的分子机制。我们发现，在FZD10过表达的滑膜肉瘤细胞中，杂乱的(Dvl)2/Dvl3复合体的磷酸化水平显著增强，rac1-JNK级联信号通路也被激活。激活FZD10-Dvls-rac1通路可诱导片状脂体形成，并促进锚定非依赖性细胞生长。FZD10的过表达还导致肌动蛋白细胞骨架结构的破坏，可能是通过下调RhoA的活性。我们的结果有力地表明，FZD10反式激活导致非规范的DVL-rac1-JNK通路的激活，并在滑膜肉瘤的发生发展中发挥关键作用。
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 down-regulation 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.