XISTの喪失は乳がん幹細胞の分化を阻害し,メディエーター過活性化により腫瘍発生性を増加させる

Laia Richart¹, Mary-Loup Picod-Chedotel², Michel Wassef¹

¹Institut Curie, PSL Research University, Sorbonne University, Paris 75005, France.

Cell

|May 21, 2022

まとめ

XISTの喪失は乳がん幹細胞の分化を阻害し,攻撃的な乳がんを促進する. XISTは乳頭上皮質のホメオスタシスを維持し,腫瘍発達の予防に不可欠です.

科学分野:

エピジェネティクス
細胞生物学
癌生物学

背景:

X不活性化 (XCI) は,XISTによって開始され,異色染色体 (Xi) が形成されます.
XCI開始後のXISTの機能は完全に理解されていません.

研究の目的:

ヒト乳がん幹細胞の分化と乳がんにおけるXISTの役割を調査する.
XISTの喪失が腫瘍発生に寄与する分子メカニズムを解明する.

主な方法:

ヒトのマスク細胞におけるXIST機能の研究
エピジェネティックの変化とXIST欠乏によるXiの遺伝子発現を分析した.
XIST欠乏性マスク細胞と乳がんにおけるMED14の役割を調査した.

主要な成果:

XISTの喪失は,MASCの分化を阻害し,高度に腫瘍発生性および転移性がんを引き起こす.
XiのXIST欠乏は,MED14を含むエピジェネティック変異と遺伝子再活性化を引き起こす.
MED14の過剰投与により,マスクの転写プログラムが乱され,分化が妨げられます.
XISTとXiの不安定性の喪失は,ヒトの乳がんの予後不良と相関しています.

結論:

XISTはヒト乳頭上皮質ホメオスタシスの重要なゲートキーパーとして機能する.
XIST欠乏症とXi転写不安定は乳がんの発生と進行に寄与する.
発見はソマティック・セル・アイデンティティ・コントロールにおける新たなパラダイムを明らかにし,ジェンダー特有の癌への影響を及ぼしている.

キーワード:

メディエーター X染色体 XIST について乳がんの発生区分する強化剤ホメオスタシスヒト乳腺幹細胞ポリコンブトランスクリプション再活性化

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