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MAT2B mediates invasion and metastasis by regulating EGFR signaling pathway in hepatocellular carcinoma

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Abstract

The poor prognosis of hepatocellular carcinoma (HCC) patients is mainly due to cancer metastasis. Methionine adenosyltransferase 2β (MAT2B) encodes a regulatory subunit (β) for methionine adenosyltransferase. Previous studies reveal that MAT2B provides a growth advantage for HCC, but its role in metastasis is unknown. This study showed that both in the xenograft zebra fish model and in the lung metastasis model in nude mice, the stable inhibition of MAT2B could suppress the metastasis of HCC cancer cells. Silencing of MAT2B in HCC cell lines could remarkably inhibit migration and invasion. By analysis of human phospho-kinase array membranes, we found several differentially expressed proteins, including phosphor-AKT, phospho-EGFR, phospho-Src family, phospho-FAK, phospho-STAT3 and phospho-ERK. We further confirmed the change of these EGFR pathway-related proteins was in accordance with MAT2B expression pattern through immunoblotting test. Finally, we found that MAT2B was overexpressed in HCC caner tissues and correlated with poor prognosis for HCC patients in clinical manifestation. Our study demonstrated that silencing of MAT2B could suppress liver cancer cell migration and invasion through the inhibition of EGFR signaling, which suggested that MAT2B might serve as a new prognostic marker and therapeutic target for HCC.

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Funding

This work was supported by grant from the National Natural Science Foundation of China ‘(81401980)’ (to Lijun Wu) and the Development Fund for Shanghai Talents ‘(201660)’ (to Dongqin Yang) and the Natural Science Foundation and Major Basic Research Program of Shanghai ‘(16JC1420104)’ (to Jie Liu).

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Authors and Affiliations

  1. Department of Digestive Diseases of Huashan Hosptial, Fudan University, Shanghai, 200040, China

    Lijun Wu, Bin Lv, Zhihui Che, Wenli Zhang, Mengmeng Wu, Jun Zhang, Dongqin Yang & Jie Liu

  2. Fudan University Library, Shanghai, 200433, China

    Lijun Wu & Jun Ying

  3. Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, 200032, China

    Ping Chen & Qi Zhang

  4. The Third Department of Hepatic Surgery of Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, 200438, China

    Fuchen Liu

Authors
  1. Lijun Wu
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  2. Ping Chen
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  3. Jun Ying
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  4. Qi Zhang
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  5. Fuchen Liu
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  6. Bin Lv
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  7. Zhihui Che
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  8. Wenli Zhang
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  9. Mengmeng Wu
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  10. Jun Zhang
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  11. Dongqin Yang
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  12. Jie Liu
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Contributions

Lijun Wu was responsible for manuscript preparation and contributed to study design and experiment process. Ping Chen contributed to the data analysis and experiment process. Dongqin Yang contributed to study design. All co-authors contributed to the data interpretation and manuscript revision. All authors approved the final version of this manuscript.

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Correspondence to Dongqin Yang or Jie Liu.

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Wu, L., Chen, P., Ying, J. et al. MAT2B mediates invasion and metastasis by regulating EGFR signaling pathway in hepatocellular carcinoma. Clin Exp Med 19, 535–546 (2019). https://doi.org/10.1007/s10238-019-00579-2

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  • DOI: https://doi.org/10.1007/s10238-019-00579-2

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