| Project/Area Number |
17K10781
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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 |
Respiratory surgery
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| Research Institution | Kyoto University |
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Principal Investigator |
Menju Toshi 京都大学, 医学研究科, 講師 (30527081)
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| Co-Investigator(Kenkyū-buntansha) |
園部 誠 京都大学, 医学研究科, 准教授 (00432378)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 肺癌 / 浸潤転移 / 上皮間葉転換、ＥＭＴ / ＥＧＦＲ / ＧＥＰ１００ / Ａｒｆ６ / Ｇｒｂ２ / 肺腺癌 / ＥＭＴ / 浸潤転移能 / EGFR陽性肺腺癌 / Grb2 / GEP100 / Arf6 / AMAP1 / EPB41L5 / EMT / EGFR / 予後不良 / Arf6活性化 / 上皮間葉転換 |
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| Outline of Final Research Achievements |
There are no therapies that directly target the invasive metastatic mechanism of lung cancer, which has an unmet medical need. While the GEP100-Arf6 pathway, a mechanism of cancer cell invasion and metastasis, has been reported so far, we have further analyzed the clinical significance and importance of these pathways associated with EMT. In this study, we further elucidated the mechanisms by which Grb2, a known EGFR-binding molecule, can enhance the GEP100-Arf6 pathway and worsen patients’ prognosis by binding to and forming a complex with GEP100 and EGFR. The elucidation of this mechanism will facilitate the development of new molecular targeting agents to inhibit invasion and metastasis.
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| Academic Significance and Societal Importance of the Research Achievements |
現在、浸潤転移能を直接標的とした薬剤はみられず、臨床的観点から最も切望されている。我々と佐邊らのグループは、この臨床的問題点を認識し、GEP100-Arf6経路という癌細胞の浸潤メカニズムの解明を世界に先駆けて研究・報告しており、さらにEGFRとGrb2-GEP100複合体の結合様式の解明により、同結合部位を標的とする浸潤転移能抑制に有効な薬剤の開発につながる。
また、当然この経路を阻害して、浸潤転移の抑制が可能となれば、腫瘍の遠隔転移制御を通じて、術後再発予防や、発見時遠隔転移症例に対する治療適応の拡大など様々な点で、既存治療法に加えて新たな癌治療戦略を採ることが可能となることが期待される。
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