Open AccessEZH2 promotes progression of small cell lung cancer by suppressing the TGF-β-Smad-ASCL1 pathway
Author(s) -
Fumihiko Murai,
Daizo Koinuma,
Aya ShinozakiUshiku,
Masashi Fukayama,
Kohei Miyaozono,
Shogo Ehata
Publication year - 2015
Publication title -
cell discovery
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.412
H-Index - 29
ISSN - 2056-5968
DOI - 10.1038/celldisc.2015.26
Subject(s) - cancer research , transforming growth factor , smad , biology , lung cancer , gene silencing , ezh2 , apoptosis , cell growth , microbiology and biotechnology , epigenetics , pathology , medicine , biochemistry , genetics , gene
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.