ROR1 functions as a scaffold of cavin-1 and CAV1, sustaining caveolae and RTK-mediated survival signaling in lung cancer
| Project/Area Number |
16K09579
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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 organ internal medicine
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| Research Institution | Kumamoto University |
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Principal Investigator |
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| Co-Investigator(Renkei-kenkyūsha) |
FUJIMOTO Toyoshi 名古屋大学, 医学系研究科, 教授 (50115929)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | 肺腺がん / ROR1 / カベオラ / EGFR-TKI / 薬剤耐性 |
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| Outline of Final Research Achievements |
ROR1 sustains prosurvival signaling directly downstream of the lineage-survival oncogene TTF-1 in lung adenocarcinoma. In this study, we report an unanticipated function of this receptor tyrosine kinase (RTK) as a scaffold of CAVIN1 and CAV1, two essential structural components of caveolae. This kinase-independent function of ROR1 facilitates the interactions of CAVIN1 and CAV1 at the plasma membrane, thereby preventing the lysosomal degradation of CAV1. Caveolae structures and prosurvival signaling towards AKT through multiple RTKs are consequently sustained. We also provide mechanistic insight into how ROR1 inhibition can overcome EGFR-tyrosine kinase inhibitor resistance due to bypass signaling via diverse RTKs such as MET and IGF-IR, which is currently a major clinical obstacle. Considering its onco-embryonic expression, inhibition of the scaffold function of ROR1 in patients with lung adenocarcinoma appears to be an attractive approach to better treating this devastating cancer.
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Report
(3 results)
Research Products
(6 results)
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[Presentation] ROR1 functions as a scaffold of cavin-1 and CAV1, sustaining caveolae and RTK-mediated survival signaling in lung cancer2016
Author(s)
Tomoya Yamaguchi, Can Lu, Lisa Ida, Kiyoshi Yanagisawa, Jiro Usukura, Yukako Shimada, Hisanori Isomura, Motoshi Suzuki, Toyoshi Fujimoto, Takashi Takahashi
Organizer
第41回内藤コンファレンス
Place of Presentation
シャトレーゼガトーキングダム札幌、日本
Year and Date
2016-07-05
Related Report
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[Presentation] ROR1 functions as a scaffold of cavin-1 and CAV1, sustaining caveolae and RTK-mediated survival signaling in lung cancer2016
Author(s)
Yamaguchi T, Lu C, Ida L, Yanagisawa K, Usukura J, Cheng J, Hotta N, Shimada Y, Isomura H, Suzuki M, Fujimoto T and Takahashi T
Organizer
AACR ANNUAL MEETING 2016
Place of Presentation
New Orleans, LA, USA
Year and Date
2016-04-16
Related Report
Int'l Joint Research
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