The transcription factor SALL4 regulates stemness of EpCAM-positive hepatocellular carcinoma

フォーマット:

論文

責任表示:

Zeng, Sha Sha ; Yamashita, Taro ; Kondo, Mitsumasa ; Nio, Kouki ; Hayashi, Takehiro ; Hara, Yasumasa ; Nomura, Yoshimoto ; Yoshida, Mariko ; Hayashi, Tomoyuki ; Oishi, Naoki ; Ikeda, Hiroko ; Honda, Masao ; Kaneko, Shuichi

言語:

英語

出版情報:

Elsevier, 2014-01-01

著者名:

Zeng, Sha Sha

Yamashita, Taro

Kondo, Mitsumasa

Nio, Kouki

Hayashi, Takehiro

Hara, Yasumasa

Nomura, Yoshimoto

Yoshida, Mariko

Hayashi, Tomoyuki

Oishi, Naoki

Ikeda, Hiroko

Honda, Masao

Kaneko, Shuichi

続きを見る

掲載情報:

Journal of Hepatology

ISSN:

0168-8278      

巻:

60

通号:

1

開始ページ:

127

終了ページ:

134

バージョン:

author

概要:

Background & Aims: Recent evidence suggests that hepatocellular carcinoma can be classified into certain molecular subtypes with distinct prognoses based on the stem/maturational status of the tumor. We investigated the transcription program deregulated in hepatocellular carcinomas with stem cell features. Methods: Gene and protein expression profiles were obtained from 238 (analyzed by microarray), 144 (analyzed by immunohistochemistry), and 61 (analyzed by … qRT-PCR) hepatocellular carcinoma cases. Activation/suppression of an identified transcription factor was used to evaluate its role in cell lines. The relationship of the transcription factor and prognosis was statistically examined. Results: The transcription factor SALL4, known to regulate stemness in embryonic and hematopoietic stem cells, was found to be activated in a hepatocellular carcinoma subtype with stem cell features. SALL4-positive hepatocellular carcinoma patients were associated with high values of serum alpha fetoprotein, high frequency of hepatitis B virus infection, and poor prognosis after surgery compared with SALL4-negative patients. Activation of SALL4 enhanced spheroid formation and invasion capacities, key characteristics of cancer stem cells, and up-regulated the hepatic stem cell markers KRT19, EPCAM, and CD44 in cell lines. Knockdown of SALL4 resulted in the down-regulation of these stem cell markers, together with attenuation of the invasion capacity. The SALL4 expression status was associated with histone deacetylase activity in cell lines, and the histone deacetylase inhibitor successfully suppressed proliferation of SALL4-positive hepatocellular carcinoma cells. Conclusions: SALL4 is a valuable biomarker and therapeutic target for the diagnosis and treatment of hepatocellular carcinoma with stem cell features. © 2013 European Association for the Study of the Liver. 続きを見る

URL:

http://hdl.handle.net/2297/36257