ROR1 sustains RTK-mediated survival signaling in lung adenocarcinoma
Project/Area Number |
25461187
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Multi-year Fund |
Section | 一般 |
Research Field |
Respiratory organ internal medicine
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Research Institution | Nagoya University |
Principal Investigator |
YAMAGUCHI TOMOYA 名古屋大学, 医学(系)研究科(研究院), 特任助教 (70452191)
|
Co-Investigator(Renkei-kenkyūsha) |
YANAGISAWA Kiyoshi 名古屋大学, 大学院医学系研究科, 講師 (20372112)
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
Keywords | 肺腺がん / ROR1 / カベオラ / EGFR-TKI / 薬剤耐性 / 肺腺癌 / TTF-1 / 受容体型チロシンキナーゼ / EGFR / RTKの活性化 / RTKのクロストーク |
Outline of Final Research Achievements |
The receptor tyrosine kinase-like orphan receptor 1 (ROR1) sustains prosurvival signaling directly downstream of the lineage-survival oncogene NKX2-1/TTF-1 in lung adenocarcinoma. We analyzed the effects of siROR1 treatment on the phosphorylation state using a human phospho-RTK array, which revealed a significant decrease in the phosphorylation of multiple RTKs in both NCI-H1975 and PC-9 lung adenocarcinoma cells. We found that ROR1 knockdown effectively overcame ligand-mediated EGFR-TKI resistance in PC-9 or NCI-H1975 cell. These results suggest that ROR1 repression inhibits lung adenocarcinoma cells with acquired EGFR-TKI resistance through bypass pathways. Finally, we also found that ROR1 knockdown significantly decreased the protein expression of CAV1, the essential structural component of caveolae, in lung adenocarcinoma cells.
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Report
(4 results)
Research Products
(9 results)
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[Journal Article] ROR1 sustains caveolae and survival signaling as a scaffold of cavin-1 and caveolin-12016
Author(s)
Yamaguchi T, Lu C, Yanagisawa K, Can Lu, Usukura J, Cheng J, Hotta N, Shimada Y, Ida R, Isomura H, Suzuki M, Fujimoto T, Takahashi T
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Journal Title
Nat Commun
Volume: 7
Issue: 1
Pages: 10060-10060
DOI
Related Report
Peer Reviewed / Open Access
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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-IASLC Joint Lung Cancer Conference
Place of Presentation
San Diego, CA, アメリカ
Year and Date
2016-01-04
Related Report
Int'l Joint Research
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