Molecular mechanisms and physiological function of amino acid endocytosis
| Project/Area Number |
18K06018
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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 42030:Animal life science-related
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| Research Institution | Yamaguchi University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | エンドサイトーシス / アミノ酸 / ダイナミン / 栄養シグナル / mTORC1 / シグナル伝達 |
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| Outline of Final Research Achievements |
mTORC1 is a major metabolic signaling complex that activates cellular biosynthesis. In this study, we found that endocytosis inhibitors suppressed cell proliferation and mTORC1 activity in various tumor-derived cell lines. It was also confirmed that endocytosis inhibitors increased the number of S-phase cells and induced apoptosis in a tumor-specific manner.
On the other hand, it has been reported that endocytosis activity increases during amino acid starvation, which is thought to be a mechanism to ensure that cells obtain necessary amino acids. Experiments using dynamin-1/2/3 triple knockout cells revealed that dynamin is involved in this phenomenon.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、がん細胞に対するエンドサイトーシス阻害剤の細胞増殖抑制作用と、がん細胞にとって重要なアミノ酸確保経路であるエンドサイトーシスの、より詳細なメカニズムが明らかとなった。エンドサイトーシス阻害剤は細胞の栄養取り込み阻害剤として働き、本研究で示されたように栄養要求性の高いがん細胞への対抗するための手段として有効である可能性がある。さらに、エンドサイトーシス活性の調節により適度な栄養取り込みの抑制が実現できれば、過栄養によって引き起こされる肥満や生活習慣病（糖尿病、高血圧、脂質異常症など）の治療薬・予防薬として有効である可能性がある。
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Report
(4 results)
Research Products
(12 results)
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[Journal Article] Autophagy regulates levels of tumor suppressor enzyme protein phosphatase 6.2020
Author(s)
Nobuyuki Fujiwara, Shusaku Shibutani, Yusuke Sakai, Toshio Watanabe, Issei Kitabayashi, Hiroko Oshima, Masanobu Oshima, Hisashi Hoshida, Rinji Akada, Tatsuya Usui, Takashi Ohama*, Koichi Sato.
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Journal Title
Cancer Science
Volume: 111
Issue: 12
Pages: 4371-4380
DOI
Related Report
Peer Reviewed / Open Access
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