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脂肪1の削除は,ハイブリッドEMT状態,腫瘍幹および転移を促進します

Ievgenia Pastushenko^1,2,3, Federico Mauri¹, Yura Song¹

¹Laboratory of Stem Cells and Cancer, Université Libre de Bruxelles (ULB), Brussels, Belgium.

|December 17, 2020

まとめ

FAT1遺伝子の機能の喪失は,ハイブリッドの上皮からメゼンキマへの移行 (EMT) 状態を促進することによって癌を加速します. これは腫瘍の発症,進行,転移に影響し,FAT1欠乏がんの新たな治療の脆弱性を明らかにしています.

科学分野:

腫瘍学
分子生物学
遺伝学

背景:

プロトカデリンをコードするFAT1は,ヒトの癌で頻繁に変異します.
腫瘍形成におけるFAT1変異の正確な役割と分子メカニズムは不明である.

研究の目的:

腫瘍の発症と進行における FAT1の機能を調査する.
ガン発症における FAT1 の役割の基礎となる分子メカニズムを解明する.

主な方法:

皮膚状細胞癌と肺腫瘍のマウスモデルを使用した.
トランスクリプション,クロマチン,プロテオミックプロファイリングを行いました.
主要な分子経路を特定するためのメカニズム研究を行いました.

主要な成果:

脂肪1の消去はマウスモデルにおける腫瘍の発症,進行,転移を加速した.
マウスとヒトの両方のFAT1欠乏性腫瘍において,ハイブリッドの上皮からメゼンキーマへの移行 (EMT) 現象が観察されました.
FAT1機能の喪失は,YAP1とZEB1を促進するCAMK2-CD44-SRC軸を活性化させ,SOX2を上調するためにEZH2を無効化し,ハイブリッドEMT状態を駆動します.
FAT1欠乏性腫瘍における薬剤耐性および脆弱性を特定した.

結論:

FAT1の機能の喪失は,状細胞癌におけるハイブリッドEMT状態を通じて腫瘍の開始,進行,侵入性,転移を促進する.
これらのメカニズムを理解することで,FAT1欠乏性がんの治療戦略の洞察が得られます.

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