| Project/Area Number |
18K15949
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 53030:Respiratory medicine-related
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| Research Institution | Nagoya University |
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Principal Investigator |
Tanaka Ichidai 名古屋大学, 医学部附属病院, 病院助教 (40809810)
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| Project Period (FY) |
2018-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | LKB1 / SMOC1 / 細胞増殖 / 移動能 / 血管新生 / 予後予測因子 / 非小細胞肺がん / 予後予測 / 非小細胞肺癌 |
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| Outline of Final Research Achievements |
Liver kinase B1 (LKB1) is a tumor suppressor frequently inactivated in some human cancers, and non-small lung cancer (NSCLC) with LKB1 inactivation is one of the most aggressive neoplasms. To identify molecular features associated with LKB1 inactivation, bioinformatic analysis was initially conducted using lung cancer omics datasets such as mRNA and protein expression. Eventually, SPARC Related Modular Calcium Binding 1 (SMOC1), which plays essential roles in both eye and limb development, was identified as a markedly increased secreted protein in LKB1-inactivated NSCLC. SMOC1 knockdown reduced cancer cell migration and tumor angiogenesis in NSCLC with LKB1 inactivation. Furthermore, SMOC1 expression was significantly associated with poor overall survival, indicating that SMOC1 expression would be one of a prognostic biomarker in MSCLC. Our findings suggest that SMOC1 plays a crucial role in the development of NSCLC with LKB1 inactivation.
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| Academic Significance and Societal Importance of the Research Achievements |
腫瘍抑制遺伝子であるLKB1は非小細胞肺癌 の約20％において不活化変異をきたしており、腫瘍の進展が早く極めて予後が悪い。本研究では、LKB1が不活化した肺癌の特徴を分子レベルで解明することを目指し、研究の成果としてSMOC1という分泌タンパクの高発現が、腫瘍の増殖・進展に寄与していることを発見した。今後は本研究を基盤に、予後の悪いLKB1が不活化した肺癌に対し、SMOC１を標的とした新たな治療戦略の構築を目指すことが可能である。
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