| Project/Area Number |
17K09644
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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 | Gunma University |
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Principal Investigator |
Sunaga Noriaki 群馬大学, 医学部附属病院, 講師 (70400778)
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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: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | 肺癌 / 非小細胞肺癌 / 肺腺癌 / Wnt経路 / Wntシグナル伝達経路 / 分子標的治療 |
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| Outline of Final Research Achievements |
LGR6 overexpression was induced by activation of the Wnt/β-catenin signaling pathway in non-small cell lung cancer (NSCLC) cells, in which tumor growth was inhibited by LGR6 knockdown. In NSCLC surgical specimens, LGR6 was significantly higher in lung adenocarcinomas with wild-type EGFR and vascular invasion-positive, and elevated LGR6 expression was an independent poor prognostic marker. To elucidate molecular mechanisms underlying LGR6-induced malignant phenotypes, we conducted microarray expression profiling of NSCLC cells with or without LGR6 knockdown. Consequently, several LGR6-associated genes including cancer stem cell markers, cytokines, and growth factors were identified. Pathway analysis of microarray data also revealed that LGR6 could regulate pathways involved in inflammation and tumor microenvironment. These results suggest that LGR6 overexpression induced by activation of the Wnt pathway contributes to an aggressive phenotype and could be a therapeutic target in NSCLC.
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| Academic Significance and Societal Importance of the Research Achievements |
肺癌は死亡率の高い癌であり、新規治療の開発が急務である。我々は、非小細胞肺癌においてWnt経路活性化により誘導されるLGR6過剰発現が、炎症誘導や腫瘍微小環境に関わるシグナル伝達経路や、癌幹細胞マーカー、サイトカイン、増殖因子などの分子を制御することで、悪性形質の獲得に寄与していることを明らかにした。また、EGFR変異陰性の肺腺癌においてLGR6高発現が予後不良と関連していることや、LGR6阻害が肺癌細胞の増殖を抑制することを見出した。本研究の結果から、LGR6が高悪性度の肺癌に対する新たな治療標的分子であり、予後予測バイオマーカーとなることが示唆された。
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