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

Michiru NishitaDivision of Cell Physiology, Department of Physiology and Cell Biology, Kobe University, Graduate School of Medicine, Kobe, 650-0017, Japan. [email protected]Seung‐Yeol ParkDivision of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, MA, 02115, USATadashi NishioDivision of Cell Physiology, Department of Physiology and Cell Biology, Kobe University, Graduate School of Medicine, Kobe, 650-0017, JapanKoki KamizakiDivision of Cell Physiology, Department of Physiology and Cell Biology, Kobe University, Graduate School of Medicine, Kobe, 650-0017, JapanZhichao WangDivision of Cell Physiology, Department of Physiology and Cell Biology, Kobe University, Graduate School of Medicine, Kobe, 650-0017, JapanKota TamadaRIKEN Brain Science Institute, Wako, 351-0198, JapanToru TakumiRIKEN Brain Science Institute, Wako, 351-0198, JapanRyuju HashimotoDepartment of Developmental Biology, Faculty of Medicine, Shimane University, Izumo, 690-8504, JapanHiroki OtaniDepartment of Developmental Biology, Faculty of Medicine, Shimane University, Izumo, 690-8504, JapanGregory J. PazourProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USAVictor W. HsuDivision of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, MA, 02115, USAYasuhiro MinamiDivision of Cell Physiology, Department of Physiology and Cell Biology, Kobe University, Graduate School of Medicine, Kobe, 650-0017, Japan. [email protected]
2017en
ABI

Аннотация

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.

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