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循環する腫瘍細胞のクラスタリングは,DNAメチル化により,転移のシッティングを可能にします
Sofia Gkountela1, Francesc Castro-Giner2, Barbara Maria Szczerba1
1Cancer Metastasis Laboratory, Department of Biomedicine, University of Basel and University Hospital Basel, 4058 Basel, Switzerland.
Cell
|January 12, 2019
まとめ
循環する腫瘍細胞 (CTC) 群は,特定のDNAメチル化変化によって癌の転移を促進する. 研究者はCTCクラスタを分解する FDAが承認した薬を特定し 癌の広がりを抑制する新しい戦略を提案しました
科学分野:
- 癌 生物学
- エピジェネティクス
- 転移に関する研究
背景:
- 循環する腫瘍細胞 (CTC) のクラスターは,転移の可能性の増加と関連しています.
- CTCクラスターの生物学的特徴と脆弱性は十分に理解されていません.
研究 の 目的:
- 単一のCTCとCTCクラスタのDNAメチル化状況を調査する.
- CTCクラスターの脆弱性や潜在的な治療目標の特定
主な方法:
- 乳がん患者およびマウスモデルからの単一のCTCおよびCTCクラスターの全ゲノムDNAメチル化プロファイリング.
- CTCクラスターの整合性を影響する物質を特定するためにFDAが承認した化合物のスクリーニング.
主要な成果:
- CTCクラスターは,幹性および増殖に関連する転写因子 (例えば,OCT4,NANOG,SOX2) の結合部位で特定の低メチル化を示す.
- Na+/K+ ATPase阻害剤は,CTCクラスタを単細胞に分解する化合物として識別された.
- CTCクラスタの解離はDNAメチル化リモデリングと転移抑制につながった.
結論:
- CTCのクラスタリングは,幹と転移を促進する表遺伝的変異と関連しています.
- Na+/K+ ATPase 阻害剤のような特定の化合物で CTC クラスタをターゲットにすると,癌の転移を抑制できます.
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