アスパラジンの生物利用性は,乳がんのモデルにおける転移を制御する

Simon R V Knott^1,2,3, Elvin Wagenblast^2,4,5, Showkhin Khan^2,6

¹Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK.

Nature

|February 8, 2018

まとめ

アスパラジン摂取は乳がんの転移に大きく影響する. このアミノ酸を制限すると,原発腫瘍の成長に影響を及ぼさず,転移を減少させ,潜在的な治療戦略を提供します.

科学分野:

腫瘍学
癌生物学
転移に関する研究

背景:

乳がんの異質性は転移の可能性に影響する.
以前の研究では,転移の誘発因子候補が特定されました.
アスパラジン合成酵素の発現は転移性再発と相関する.

研究の目的:

乳がんの転移におけるアスパラジン生物学的利用の役割を調査する.
アスパラジンの濃度が転移の進行と侵襲性の可能性に影響するかどうかを判断する.

主な方法:

機能性乳がんモデルと微分発現分析
実験室内および体内のRNA干渉スクリーニング
アスパラジン合成酵素発現の操作と食事によるアスパラジン制限
侵襲的可能性と上皮からメゼンキマへの移行マーカーの評価

主要な成果:

アスパラジンの生物利用性は,転移の可能性に強く影響する.
アスパラジンの濃度を下げる (ノックダウン,l- アスパラギナーゼ,または食事) により転移が減少した.
アスパラジン濃度の上昇は転移を促した.
アスパラジンの可用性の変化は,上皮からメゼンキマへの移行に関与するタンパク質に影響した.

結論:

アスパラジンは乳がんの転移の重要な調節因子です.
アスパラジンの代謝をターゲットにすることは,転移を減らすための潜在的な治療戦略です.
甲状腺からメゼンキマへの移行経路は,アスパラジン媒介の転移の調節に関与しています.

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