Ligand-independent roles of ErbB recepotors on the regulation of cell-cell adhesion
| Project/Area Number |
16K07119
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Oita University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
石崎 敏理 大分大学, 医学部, 教授 (70293876)
橋本 悟 名古屋大学, 環境医学研究所, 特任准教授 (60352150)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Keywords | 上皮細胞極性 / 腫瘍形成 / 癌悪性化 / ErbB受容体ファミリー / 上皮細胞恒常性 / 腫瘍悪性化 / 細胞間接着 / エンドサイトーシス / 微小管 / チロシンキナーゼ |
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| Outline of Final Research Achievements |
Internalisation and trafficking of activated receptor tyrosine kinases (RTKs) determines duration and spatial distribution of growth factor signalling. Here we show that the ErbB3 receptor acts in a ligand-independent manner to sort cell-surface proteins for endocytic recycling in breast epithelial cells. Loss of ErbB3 abrogates recycling of integrins from a Rab4-positive compartment and redirects it towards degradation. Consequently, delivery of integrins to the leading front of migrating epithelial cells is impaired and cell migration compromised upon loss of ErbB3. Mechanistically, ErbB3 interacts and stabilises the Rab4/5 effector rabaptin5 and the endosomal adaptor GGA3 thereby facilitating assembly of the Arf6-GGA3-rabaptin5 complex, required for recycling of cargo including integrins. We show that ErbB3 is an integral part in the endosomal trafficking machinery, provoking the notion that RTKs might play a more instrumental role in vesicular trafficking than commonly perceived.
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| Academic Significance and Societal Importance of the Research Achievements |
細胞間接着形成に関与する様々なシグナル伝達が明らかになっているが、多くは細胞間接着形成の過程の一部分に焦点をあてたものであり、細胞間接着形成全体を包括的に制御する因子については、未だその知見が乏しい。本研究では非リン酸化型ErbB3の細胞間接着形成統括因子としての機能確立を目指したものであり、細胞間接着形成、さらに腫瘍悪性化の新たな分子機序の解明につながると考えている。また、非リン酸化型受容体によるシグナル伝達は、他の受容体チロシンキナーゼにも存在する可能性は高い。がん細胞の薬剤耐性獲得の機序を解き明かす新たな鍵となる可能性があり、新規癌分子標的薬の開発に向けた礎となり得るものである。
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Report
(4 results)
Research Products
(26 results)
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[Journal Article] PI3K regulates endocytosis after insulin secretion by mediating signaling crosstalk between Arf6 and Rab27a2016
Author(s)
Yamaoka M, Ando T, Terabayashi T, Okamoto M, Takei M, Nishioka T, Kaibuchi K, Matsunaga K, Ishizaki R, Izumi T, Niki I, Ishizaki T, Kimura T
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Journal Title
Journal of Cell Science
Volume: 129
Issue: 3
Pages: 637-649
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Role of Rho-mDia1 Signaling to Maintain Cardiac Function in Response to Pressure Overload in Mice.2018
Author(s)
Abe I., Teshima Y., Yonehara Y., Kaku H., Kira S., Oniki T., Ikebe Y., Kondo H., Saito S., Terabayashi T., Ishizaki T., and Takahashi N.
Organizer
第82回日本循環器学会
Related Report
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[Presentation] Role of Rho-mDia1 Signaling in the Pressure Overload-Induced Cardiac Hypertrophic Response.2017
Author(s)
Abe I., Teshima Y., Yonehara Y., Kaku H., Kira S., Oniki T., Ikebe Y., Kondo H., Saito S., Terabayashi T., Ishizaki T., and Takahashi N.
Organizer
第81回日本循環器学会学術集会
Place of Presentation
石川県立音楽堂 石川県金沢市
Related Report
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