Maelstrom Promotes Hepatocellular Carcinoma Metastasis by Inducing Epithelial-Mesenchymal Transition by Way of Akt/GSK-3β/Snail Signaling

被引：124

作者：

Liu, Lulu ^{[1
]}

Dai, Yongdong ^{[1
]}

Chen, Jinna ^{[2
,3
]}

Zeng, Tingting ^{[1
]}

Li, Yan ^{[1
,2
,3
]}

Chen, Leilei ^{[2
,3
]}

Zhu, Ying-Hui ^{[1
]}

Li, Jiangchao ^{[4
]}

Li, Yan ^{[1
,2
,3
]}

Ma, Stephanie ^{[2
,3
]}

Xie, Dan ^{[1
]}

Yuan, Yun-Fei ^{[1
]}

Guan, Xin-Yuan ^{[1
,2
,3
]}

机构：

[1] Sun Yat Sen Univ, Ctr Canc, State Key Lab Oncol South China, Guangzhou 510275, Guangdong, Peoples R China

[2] Univ Hong Kong, Dept Clin Oncol, Pokfulam, Hong Kong, Peoples R China

[3] Univ Hong Kong, State Key Lab Liver Res, Pokfulam, Hong Kong, Peoples R China

[4] Guangdong Pharmaceut Univ, Vasc Biol Res Inst, Guangzhou, Guangdong, Peoples R China

来源：

HEPATOLOGY | 2014年 / 59卷 / 02期

关键词：

COMPARATIVE GENOMIC HYBRIDIZATION; MOUSE MAELSTROM; STEM-CELLS; PATHWAY; GENE; PIWI; IDENTIFICATION; PATHOGENESIS; PROGRESSION; MICRORNA-7;

D O I：

10.1002/hep.26677

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Amplification of 1q is one of the most frequent chromosomal alterations in human hepatocellular carcinoma (HCC). In this study we identified and characterized a novel oncogene, Maelstrom (MAEL), at 1q24. Amplification and overexpression of MAEL was frequently detected in HCCs and significantly associated with HCC recurrence (P = 0.031) and poor outcome (P = 0.001). Functional study demonstrated that MAEL promoted cell growth, cell migration, and tumor formation in nude mice, all of which were effectively inhibited when MAEL was silenced with short hairpin RNA (shRNAs). Further study found that MAEL enhanced AKT activity with subsequent GSK-3 phosphorylation and Snail stabilization, finally inducing epithelial-mesenchymal transition (EMT) and promoting tumor invasion and metastasis. In addition, MAEL up-regulated various stemness-related genes, multidrug resistance genes, and cancer stem cell (CSC) surface markers at the messenger RNA (mRNA) level. Functional study demonstrated that overexpression of MAEL increased self-renewal, chemoresistance, and tumor metastasis. Conclusion: MAEL is an oncogene that plays an important role in the development and progression of HCC by inducing EMT and enhancing the stemness of HCC. (Hepatology 2014;59:531-543)

引用

页码：531 / 543

页数：13

共 27 条

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