2020 Fiscal Year Final Research Report
The functional analysis of LRRFIP1 in cancer infiltration, metastasis, and chemoresistance.
| Project/Area Number |
18K08696
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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 55020:Digestive surgery-related
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| Research Institution | Tohoku University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
深瀬 耕二 東北大学, 医学系研究科, 大学院非常勤講師 (00578677)
元井 冬彦 東北大学, 医学系研究科, 准教授 (30343057)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | LRRFIP1 / 膵癌 / Wnt signal / EMT / gemcitabine / JNK |
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| Outline of Final Research Achievements |
Wnt signal activator LRRFIP1 is important in regulation of EMT in pancreatic cancer cells. LRRFIP1 has been suggested to implicate in gemcitabine sensitivity by regulating EMT. In this project, we revealed LRRFIP1 silencing accelerates gemcitabine-induced cell death in pancreatic cancer cells. It was also revealed that gemcitabine-induced phosphorylation of JNK and c-Jun were increased in LRRFIP1 knockdown cells. The activation of JNK/c-Jun in LRRFIP1-knockdown cells was significantly diminished by the inhibition of Rac activity. It was confirmed that the acquisition of gemcitabine sensitivity by LRRFIP1 silencing largely depends on the stimulation of JNK/SAPK signaling. Our findings suggest that reversing EMT and transient activation of JNK might be essential for the gemcitabine sensitivity in LRRFIP1 knockdown pancreatic cancer cells. Our discoveries highlight the potential role of LRRFIP1 in the chemosensitivity related to the regulation of EMT signaling.
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| Free Research Field |
消化器外科学
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| Academic Significance and Societal Importance of the Research Achievements |
本研究では、膵癌細胞においてLRRFIP1の発現を抑制することによりゲムシタビン抗癌剤感受性が増強することを解明した。LRRFIP1発現抑制癌細胞ではJNK/SAPKシグナルの活性化が亢進していたことから、そのシグナルを制御することでゲムシタビン感受性に深く関与していると考えられた。LRRFIP1の発現、機能亢進はEMTの制御に深く関与することから、癌微小環境下におけるその発現量の変化が、抗癌剤感受性に影響している可能性が示唆される。癌微小環境下におけるLRRFIP1の発現制御、EMTの制御と抗癌剤感受性についてさらに詳細に解明することで、新たな分子標的治療開発など臨床応用が期待される。
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