2023 Fiscal Year Final Research Report
TRIB1 promotes metastasis through transcriptional activation of EMT-related genes
| Project/Area Number |
21K07095
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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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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | University of Yamanashi |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | TRIB1 / C/EBPα / TGF-β / Smad3 / がん幹細胞性 / EMT / 転移・浸潤 |
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| Outline of Final Research Achievements |
In this research, we investigated the significance of TRIB1, a gene associated with leukemia, in solid tumors. We generated TRIB1-KO cells in the human lung cancer cell line A549 using genome editing and reintroduced various TRIB1 mutants to explore its cellular and in vivo functions in cancer progression. Our findings revealed that the activation of the MAP kinase pathway and the degradation of C/EBPα by TRIB1 were necessary for anchorage independent growth and lung engraftment after tail vein injection in nude mice. These results suggest that TRIB1 may be a promising therapeutic target for solid tumors.
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| Free Research Field |
腫瘍学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究ではTRIB1が急性骨髄性白血病だけでなく，肺がんなどの難治性固形がんにおいても重要な役割を持つことを明らかにした．特に転写因子C/EBPαについては，これまで血球系細胞や脂肪細胞分化以外での機能は不明な点が多かったが，本研究結果によりTRIB1によるC/EBPαの分解が肺がん細胞の悪性化に必要であることが明らかになり，将来的な治療標的となる可能性を示すものとなった．
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