2020 Fiscal Year Final Research Report
Studies on the function and mutations of DLL3 in small cell lung cancer
| Project/Area Number |
19K23903
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Multi-year Fund |
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| Review Section |
0901:Oncology and related fields
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| Research Institution | Hokkaido University |
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Principal Investigator |
Furuta Megumi 北海道大学, 大学病院, 医員 (00848765)
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| Project Period (FY) |
2019-08-30 – 2021-03-31
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| Keywords | DLL3の機能 / 小細胞肺癌 |
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| Outline of Final Research Achievements |
To investigate the role of DLL3 in tumorigenesis in SCLC, we performed loss-of-function and gain-of-function assays using SCLC cell lines. In vitro analysis of cell migration and invasion by transwell assay showed that DLL3 knockdown reduced migration and invasion of SCLC cells, whereas DLL3 overexpression increased these activities. In addition, DLL3 positively regulated SNAI1 expression and knockdown of SNAI1 attenuated the migration and invasion ability of SCLC cells. Moreover, upregulated DLL3 expression induced subcutaneous tumor growth in mouse models. These results indicate that DLL3 promoted tumor growth, migration and invasion in an SCLC model by modulating SNAI1/Snail.
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| Free Research Field |
呼吸器腫瘍
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| Academic Significance and Societal Importance of the Research Achievements |
小細胞肺癌ではNotchのリガンドの一つであるDelta-like protein 3（DLL3）はin vitro、in vivoにおいて腫瘍増殖能、遊走能、浸潤能を促進していた。遊走能、浸潤能促進の機序としてNOTCH1非依存性に上皮間葉転換を誘導に関与する転写因子であるSnailが関与している可能性が考えられた。DLL3を標的とした治療は転移例や再発例において期待されると考えられた。
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