ネットワークを攻撃する突然変異のキノーム全体の解読 がん信号の再配線
Pau Creixell1, Erwin M Schoof1, Craig D Simpson2
1Department of Systems Biology, Technical University of Denmark, 2800 Lyngby, Denmark.
Cell
|September 22, 2015
まとめ
研究者たちは癌における ネットワーク攻撃性突然変異 (NAM) を特定し,突然変異が細胞の信号伝達を 妨げる新たな方法を明らかにした. この発見は 癌のネットワークを治療的に ターゲットにするための より良い方法につながるかもしれません
科学分野:
- 腫瘍学
- 分子生物学
- バイオ情報学
背景:
- がん細胞は 細胞の信号伝達ネットワークを 破壊する変異を蓄積することで 異常な特徴を 形成します
- これらの変異と信号伝達経路への影響を 総合的に分析することは依然として課題です
研究 の 目的:
- 癌の病理的表型を駆動するネットワーク攻撃性変異 (NAM) を特定し,特徴づけること.
- 癌変異と信号伝達ネットワークへの影響を体系的に分析するための計算ツールを開発し,適用する.
主な方法:
- 6種類のNAMを識別するためのコンピューティングプラットフォームReKINectを開発しました.
- 卵巣がん細胞系とグローバルがんゲノムリポジトリから解析されたエクソームと定量 (フォスフォ-) プロテオーム.
- 特定キナーゼ変異を含む,実験的に検証された特定されたNAM.
主要な成果:
- キナーゼ/SH2調節,ネットワーク再配線,およびリン酸化部位の変化を含む6つのNAMのクラスを特定した.
- 変異した分子論理ゲートと フォスフォトレオニン信号へのシグナルシフトと 弱体化フォスフォリレーションモチーフを発見した
- PKCγ M501IとPKD1 D665Nのような特定のNAMを検証した.
結論:
- ReKINectプラットフォームは,複雑ながんゲノムとシグナリングネットワークを介して機能的なNAMを効果的に識別します.
- これらの発見は,がん特有の分子論理の洞察を提供し,標的型がん治療の可能性を秘めています.
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