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首页> 外文期刊>Cell discovery. >EZH2 promotes progression of small cell lung cancer by suppressing the TGF-β-Smad-ASCL1 pathway
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EZH2 promotes progression of small cell lung cancer by suppressing the TGF-β-Smad-ASCL1 pathway

机译：EZH2通过抑制TGF-β-Smad-ASCL1途径促进小细胞肺癌的进展

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摘要

Transforming growth factor-β (TGF-β) induces apoptosis in many types of cancer cells and acts as a tumor suppressor. We performed a functional analysis of TGF-β signaling to identify a molecular mechanism that regulated survival in small cell lung cancer cells. Here, we found low expression of TGF-β type II receptor (TβRII) in most small cell lung cancer cells and tissues compared to normal lung epithelial cells and normal lung tissues, respectively. When wild-type TβRII was overexpressed in small cell lung cancer cells, TGF-β suppressed cell growth in vitro and tumor formation in vivo through induction of apoptosis. Components of polycomb repressive complex 2, including enhancer of zeste 2 (EZH2), were highly expressed in small cell lung cancer cells; this led to epigenetic silencing of TβRII expression and suppression of TGF-β-mediated apoptosis. Achaete-scute family bHLH transcription factor 1 (ASCL1; also known as ASH1), a Smad-dependent target of TGF-β, was found to induce survival in small cell lung cancer cells. Thus, EZH2 promoted small cell lung cancer progression by suppressing the TGF-β-Smad-ASCL1 pathway.
机译：转化生长因子-β（TGF-β）在许多类型的癌细胞中诱导凋亡，并起着抑癌作用。我们进行了TGF-β信号转导的功能分析，以确定调节小细胞肺癌细胞存活的分子机制。在这里，我们发现大多数小细胞肺癌细胞和组织中TGF-βII型受体（TβRII）的表达分别低于正常肺上皮细胞和正常肺组织。当野生型TβRII在小细胞肺癌细胞中过表达时，TGF-β通过诱导凋亡来抑制体外细胞生长和体内肿瘤形成。 polycomb抑制复合物2的成分，包括zeste 2（EZH2）的增强子，在小细胞肺癌细胞中高表达。这导致TβRII表达的表观遗传沉默和TGF-β介导的细胞凋亡的抑制。发现了Achaete-scute家族bHLH转录因子1（ASCL1;也称为ASH1），它是Smad依赖性的TGF-β靶标，可诱导小细胞肺癌细胞存活。因此，EZH2通过抑制TGF-β-Smad-ASCL1途径促进小细胞肺癌的进展。

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