Maelstrom promotes hepatocellular carcinoma metastasis by inducing epithelial-mesenchymal transition by way of Akt/GSK-3β/Snail signaling

Authors

  • Lulu Liu,

    1. State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
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    • These authors contributed equally to this work.

  • Yongdong Dai,

    1. State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
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    • These authors contributed equally to this work.

  • Jinna Chen,

    1. Department of Clinical Oncology, University of Hong Kong, Pokfulam, Hong Kong, China
    2. State Key Laboratory for Liver Research, University of Hong Kong, Pokfulam, Hong Kong, China
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  • Tingting Zeng,

    1. State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
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  • Yan Li,

    1. Department of Clinical Oncology, University of Hong Kong, Pokfulam, Hong Kong, China
    2. State Key Laboratory for Liver Research, University of Hong Kong, Pokfulam, Hong Kong, China
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  • Leilei Chen,

    1. Department of Clinical Oncology, University of Hong Kong, Pokfulam, Hong Kong, China
    2. State Key Laboratory for Liver Research, University of Hong Kong, Pokfulam, Hong Kong, China
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  • Ying-Hui Zhu,

    1. State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
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  • Jiangchao Li,

    1. Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, China
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  • Yan Li,

    1. State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
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  • Stephanie Ma,

    1. Department of Clinical Oncology, University of Hong Kong, Pokfulam, Hong Kong, China
    2. State Key Laboratory for Liver Research, University of Hong Kong, Pokfulam, Hong Kong, China
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  • Dan Xie,

    1. State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
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  • Yun-Fei Yuan,

    1. State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
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  • Xin-Yuan Guan

    Corresponding author
    1. State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, China
    2. Department of Clinical Oncology, University of Hong Kong, Pokfulam, Hong Kong, China
    3. State Key Laboratory for Liver Research, University of Hong Kong, Pokfulam, Hong Kong, China
    • Address reprint requests to: Xin-Yuan Guan, Room 605, 651 East Dongfeng Road, Guangzhou 510060, China. E-mail: xyguan@hkucc.hku.hk.

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Errata

This article is corrected by:

  1. Errata: Correction: Maelstrom promotes hepatocellular carcinoma metastasis by inducing epithelial-mesenchymal transition via Akt/GSK-3β/snail signaling Volume 63, Issue 3, 1064, Article first published online: 22 February 2016

  • Potential conflict of interest: Nothing to report.

Abstract

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-3β 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)

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