Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness.

Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness.
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DOI:
10.1038/s41598-016-0028-x
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发表时间:
2017-01-26
期刊:
影响因子:
4.6
通讯作者:
Minami Y
Minami Y
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Nishita M;Park SY;Nishio T;Kamizaki K;Wang Z;Tamada K;Takumi T;Hashimoto R;Otani H;Pazour GJ;Hsu VW;Minami Y

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通过Ror2受体酪氨酸激酶的信号转导促进肿瘤侵袭的不定形的形成。在这里,我们确定鞭毛内转运蛋白20(IFT20)是该信号在缺乏初级纤毛的肿瘤中的新靶点,并发现IFT20介导了Ror2信号诱导这些肿瘤侵袭性的能力。我们还发现IFT20通过影响GM130-AKAP450复合体来调节高尔基体来源的微管的成核,从而促进高尔基体带的形成,从而实现细胞迁移和侵袭的极化分泌。此外,IFT20提高了通过高尔基建筑群的运输效率。这些发现为Ror2信号如何促进肿瘤侵袭性提供了新的见解,并促进了对高尔基体结构和运输如何调控的理解。
Signaling through the Ror2 receptor tyrosine kinase promotes invadopodia formation for tumor invasion. Here, we identify intraflagellar transport 20 (IFT20) as a new target of this signaling in tumors that lack primary cilia, and find that IFT20 mediates the ability of Ror2 signaling to induce the invasiveness of these tumors. We also find that IFT20 regulates the nucleation of Golgi-derived microtubules by affecting the GM130-AKAP450 complex, which promotes Golgi ribbon formation in achieving polarized secretion for cell migration and invasion. Furthermore, IFT20 promotes the efficiency of transport through the Golgi complex. These findings shed new insights into how Ror2 signaling promotes tumor invasiveness, and also advance the understanding of how Golgi structure and transport can be regulated.