NLRC3は,がんにおけるPI3K-mTOR経路の抑制センサーである
Rajendra Karki1, Si Ming Man1, R K Subbarao Malireddi1
1Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Nature
|December 13, 2016
まとめ
ヌクレオチド結合領域とルシンの豊富なリピート (NLR) タンパク質は免疫と炎症を調節する. NLRC3の喪失は,mTOR経路の活性化を促すことで,大腸炎や大腸直腸がんへの感受性を高めます.
科学分野:
- 免疫学
- 分子生物学
- 胃腸内科
背景:
- ヌクレオチド結合ドメインとルシンに富んだリピート (NLR) は免疫とホメオスタシスにとって重要な細胞質センサーである.
- NLRの調節不良は炎症性,自己免疫性,がん性疾患に寄与する.
- NLRC3は,悪質に特徴づけられたNLRであり,大腸がん組織ではダウンレギュレーションされます.
研究 の 目的:
- 腸内ホメオスタシスと結腸癌の発達におけるNLRC3の役割を調査する.
- NLRC3が細胞経路を調節する分子メカニズムを解明する.
- 癌予防におけるNLRC3の治療の可能性を決定する.
主な方法:
- NLRC3欠乏したマウスを生成し,分析した.
- 大腸炎と結腸直腸腫瘍発生に対する感受性の評価
- 腸細胞におけるPI3K/AKT/mTORシグナル伝達経路とのNLRC3の相互作用を調査した.
主要な成果:
- NLRC3欠乏したマウスは大腸炎や大腸直腸がんに罹患しやすい.
- NLRC3は主にmTORシグナル伝達,細胞増殖,オーガノイド形成を抑制する.
- NLRC3はPI3Kと関連し,成長因子とトール型受容体4の信号伝達の下流のAKT活性化を阻害する.
結論:
- NLRC3は,腸内皮質におけるPI3K/ AKT/ mTOR経路の重要な阻害剤として作用する.
- NLRC3は,大腸炎や大腸直腸がんの発生に対する保護的役割を果たします.
- NLRC3をターゲットにすることで,大腸がんの予防と治療に新たな戦略が提供されるかもしれません.
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