SOX17 antagonizes WNT/β-catenin signaling pathway in hepatocellular carcinoma

被引：128

作者：

Jia, Yan ^{[1
,2
]}

Yang, Yunsheng ^{[1
]}

Liu, Shuang ^{[3
]}

Herman, James G. ^{[4
]}

Lu, Fengmin ^{[5
]}

Guo, Mingzhou ^{[1
]}

机构：

[1] Chinese Peoples Liberat Army Gen Hosp, Dept Gastroenterol & Hepatol, Beijing, Peoples R China

[2] Nankai Univ, Coll Med, Tianjin 300071, Peoples R China

[3] Capital Med Univ, Beijing Youan Hosp, Beijing, Peoples R China

[4] Sidney Kimmel Comprehens Canc Ctr Johns Hopkins, Baltimore, MD USA

[5] Peking Univ, Hlth Sci Ctr, Dept Microbiol, Beijing 100871, Peoples R China

来源：

EPIGENETICS | 2010年 / 5卷 / 08期

关键词：

DNA methylation; hepatocellular carcinoma; SOX17; 5-aza-2 '-deoxycytidine; WNT signaling pathway; BETA-CATENIN; EPIGENETIC INACTIVATION; MOLECULAR PATHOGENESIS; ALPHA-CATENIN; CANCER; EXPRESSION; METHYLATION; IDENTIFICATION; TRANSCRIPTION; ACTIVATION;

D O I：

10.4161/epi.5.8.13104

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

SRY-box containing gene 17 (SOX17) was reported to be indispensable for embryonic development and a candidate tumor suppressor gene which antagonizes the canonical WNT/beta-catenin signaling pathway in colorectal cancer. In this study, we investigated the function and epigenetic regulation of SOX17 in human hepatocellular carcinoma (HCC). DNA methylation of SOX17 was analyzed in 62 human HCC tissues and HCC cell lines by MSP. A role as a tumor suppressor gene was evaluated by colony formation assay and regulation of WNT/beta-catenin signal pathway by SOX17 was determined by IHC and luciferase reporter assay. DNA methylation of the SOX17 promoter region occurs in 82% of HCC tissues and is associated with nuclear accumulation of beta-catenin. Restoration of SOX17 inhibits HepG2 colony formation and beta-catenin/TCF-dependent transcription with the presence of HMG box in SOX17. In conclusion, SOX17 negatively regulates canonical WNT/beta-catenin signaling pathway and inhibits human HCC cells growth, providing an explanation for the loss of expression by epigenetic mechanisms in these tumors.

引用

页码：743 / 749

页数：7

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