2021 Fiscal Year Final Research Report
Identification of target molecules of differentiation inducing factor-1 in mammalian cells
Project/Area Number |
20K22709
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Multi-year Fund |
Review Section |
0801:Pharmaceutical sciences and related fields
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Research Institution | Kyushu University |
Principal Investigator |
Tetsuo Fumi 九州大学, 医学研究院, 助教 (80875899)
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Project Period (FY) |
2020-09-11 – 2022-03-31
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Keywords | DIF-1 / AMPK / mTORC1 / S6K / トリプルネガティブ乳癌 |
Outline of Final Research Achievements |
We have previously shown that DIF-1 inhibited tumor growth by regulating mTOR / S6K. From this result, it was predicted that the target of DIF-1 exists in the AMPK signaling pathway. This study investigated the effect of DIF-1 on AMPK signaling molecules using breast cancer cells. DIF-1 led to the phosphorylation (activation) of AMPK (Thr172) and phosphorylation (inactivation) of Raptor (Ser792), which is a direct substrate of AMPK, and dephosphorylation (inactivation) of p70S6K (Thr389), a major substrate of mTORC1. DIF-1 suppresses both TNBC growth and metastasis through a common signaling pathway, the AMPK-mTORC1 system. This study further strengthened our view that DIF-1 is a promising lead compound for the development of novel anticancer drugs.
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Free Research Field |
薬理学分野
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Academic Significance and Societal Importance of the Research Achievements |
がんは既存の治療薬に耐性を獲得し、遠隔転移といったがん進行を許すことで著しく生命予後を悪化させる。それゆえ、抗転移効果も含んだ新規抗腫瘍薬の開発が求められている。細胞性粘菌分化誘導因子 DIF-1は、細胞性粘菌 Dictyostelium discoideum が分泌し、柄細胞への分化を誘導する物質として単離・精製された低分子化合物である。DIF-1は蛋白質合成に重要なS6Kを調節するAMPKを活性化することで、細胞増殖抑制、細胞遊走・浸潤抑制効果を発揮することを見出した。DIF-1のターゲット分子を同定し、正確な作用機序を解明することで、抗腫瘍薬としての臨床応用への期待が高まる。
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