パン-ErbB陰性調節体Lrig1は,腫瘍抑制剤として機能する腸の幹細胞マーカーです
Anne E Powell1, Yang Wang, Yina Li
1Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Cell
|April 3, 2012
まとめ
Lrig1は,損傷した組織を補充する静止した腸の幹細胞をマークします. Lrig1の喪失は,ErbBのシグナル伝達を妨害し,腸内アデノマを引き起こし,腫瘍の予防におけるLrig1の役割を強調する.
科学分野:
- 細胞生物学 細胞生物学
- 胃腸内科 胃腸内科
- がん研究 がん研究
背景:
- 腸内幹細胞 (ISC) は,組織ホメオスタシスにとって極めて重要です.
- 増殖型 (Lgr5+) と静止型ISCの双方が存在する.
- ISCの静止状態を調節する分子機構は完全に理解されていません.
研究 の 目的:
- 静止している腸の幹細胞の分子マーカーを特定するために.
- 腸の幹細胞の調節におけるLrig1の役割を明らかにする.
- Lrig1,ErbBシグナル伝達と腸内腫瘍症の関連性を調査する.
主な方法:
- ネズミのモデルにおける系統追跡と細胞追跡.
- 大腸幹細胞のLrig1+およびLgr5+のトランスクリプトームプロファイリング.
- 遺伝子操作 (Apc 喪失,Lrig1 切除) と腫瘍形成の分析.
主要な成果:
- Lrig1は,静止状態の長寿ISCの集団を暗号のベースで特定しています.
- Lrig1+ ISCは,細胞サイクル抑制と酸化ストレス反応に関連する独特の遺伝子発現プロファイルを示しています.
- Lrig1の喪失は,ErbBのシグナル伝達の増加につながり,12小節腺腫の形成を促進します.
- Lrig1+細胞におけるApcの喪失は,腸腺腫を誘発する.
結論:
- Lrig1は腸の幹細胞の静止の重要なレギュレータである.
- Lrig1のようなネガティブレギュレータの影響を受けた,校正されたErbBシグナリングは,ISC静止状態を維持します.
- Lrig1媒介の調節の障害は,腸がんの発症を誘発する.
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