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Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness
Michiru Nishita1, Seung-Yeol Park2, Tadashi Nishio3
1Division of Cell Physiology, Department of Physiology and Cell Biology, Kobe University, Graduate School of Medicine, Kobe, 650-0017, Japan. nishita@med.kobe-u.ac.jp.
Abstract:
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.
Insights
Intraflagellar transport 20 (IFT20) is a new target of Ror2 signaling in tumors. IFT20 promotes tumor invasion by regulating Golgi structure and transport, offering new therapeutic targets.
Area of Science:
- Cell Biology
- Cancer Research
- Molecular Biology
Background:
- Ror2 receptor tyrosine kinase signaling drives invadopodia formation and tumor invasion.
- The role of Ror2 signaling in tumors lacking primary cilia is not fully understood.
Purpose of the Study:
- To identify novel targets of Ror2 signaling in tumor invasion.
- To elucidate the mechanism by which Ror2 signaling promotes tumor invasiveness in non-ciliated tumors.
Main Methods:
- Investigated the interaction between Ror2 signaling and intraflagellar transport 20 (IFT20).
- Examined the regulation of Golgi-derived microtubules and Golgi ribbon formation by IFT20.
- Assessed the impact of IFT20 on Golgi transport efficiency and tumor cell invasion.
Main Results:
- IFT20 was identified as a novel target of Ror2 signaling in tumors lacking primary cilia.
- IFT20 mediates Ror2-induced tumor invasiveness by regulating Golgi-derived microtubule nucleation via the GM130-AKAP450 complex.
- IFT20 promotes Golgi ribbon formation, polarized secretion, and enhances Golgi transport efficiency.
Conclusions:
- Ror2 signaling promotes tumor invasiveness through IFT20, which regulates Golgi structure and transport.
- IFT20 represents a key mediator in Ror2-driven tumor cell migration and invasion.
- These findings provide new insights into Ror2 signaling pathways and Golgi complex regulation in cancer.
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