Ror2 signaling regulates Golgi structure and transport through IFT20 for tumor invasiveness
Michiru Nishitaa b✉, Seung‐Yeol Parkc, Tadashi Nishiob, Koki Kamizakib, Zhichao Wangb, Kota Tamadad, Toru Takumid, Ryuju Hashimotoe, Hiroki Otanie, Gregory J. Pazourf, Victor W. Hsuc, Yasuhiro Minamib g✉
- aDivision 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
- bDivision of Cell Physiology, Department of Physiology and Cell Biology, Kobe University, Graduate School of Medicine, Kobe, 650-0017, Japan
- cDivision of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, and Department of Medicine, Harvard Medical School, Boston, MA, 02115, USA
- dRIKEN Brain Science Institute, Wako, 351-0198, Japan
- eDepartment of Developmental Biology, Faculty of Medicine, Shimane University, Izumo, 690-8504, Japan
- fProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA
- gDivision of Cell Physiology, Department of Physiology and Cell Biology, Kobe University, Graduate School of Medicine, Kobe, 650-0017, Japan. minami@kobe-u.ac.jp
- ✉Corresponding author
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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.
TL;DRIt is found that intraflagellar transport 20 mediates the ability of Ror2 signaling to induce the invasiveness of tumors that lack primary cilia, and IFT20 regulates the nucleation of Golgi-derived microtubules by affecting the GM130-AKAP450 complex. (Semantic Scholar)