異なるEMTプログラムは,正常な乳がん幹細胞と腫瘍を誘発する細胞を制御する

Xin Ye¹, Wai Leong Tam^1,2,3, Tsukasa Shibue¹

¹Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA.

|September 3, 2015

まとめ

腫瘍発起細胞 (TIC) と正常幹細胞は,それぞれスラグとスナイルによって調節される異なる上皮からメゼンキマへの移行 (EMT) プログラムを使用する. これらの発見は癌の転移と正常な組織機能の基礎となる幹細胞プログラムにおける重要な違いを明らかにしています

科学分野:

癌生物学
幹細胞研究
分子腫瘍学

背景:

腫瘍を誘発する細胞 (TIC) は癌の転移と再発を誘発する.
TICは活性化された正常組織幹細胞から生じるという仮説がある.
転写因子Slugは正常な乳がん幹細胞活動を調節する.

研究の目的:

TIC生成の基礎となる分子機構を調査する.
普通の乳がん幹細胞とTICの幹細胞プログラムを比較する
異なる幹細胞集団におけるスラグとスナイルの役割を明らかにする.

主な方法:

遺伝子組み換えの記者マウスを使った
基礎層の乳腺幹細胞と光層のTICを分析した.
スラグとスナイルのEMT-TFの表現と機能を調査した.

主要な成果:

普通の乳がん幹細胞はスラグを使いますが乳がん幹細胞はスナイルを使います
これらのパラログな転写因子は,異なる上皮からメゼンキマへの移行 (EMT) プログラムを引き起こす.
ガン幹細胞と正常な細胞における EMT プログラムの差異的利用が実証された.

結論:

TICの幹細胞プログラムと正常な幹細胞は同一ではありません
スラグとスナイルは異なる乳腺細胞集団で異なるEMTプログラムを実行します
発見は,がんの進行と正常な組織ホメオスタシスの重要な分子の違いを強調しています.

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