Estrogen-sensitive PTPRO expression represses hepatocellular carcinoma progression by control of STAT3

Authors

  • Jiajie Hou,

    1. Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
    2. The Key Laboratory of Living Donor Liver Transplantation, Ministry of Health, Nanjing, China
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    • These authors contributed equally to this work.

  • Juan Xu,

    1. The State Key Laboratory of Pharmaceutical Biotechnology, Molecular Immunology and Cancer Research Center, School of Life Sciences, Nanjing University, Nanjing, China
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    • These authors contributed equally to this work.

  • Runqiu Jiang,

    1. Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
    2. The Key Laboratory of Living Donor Liver Transplantation, Ministry of Health, Nanjing, China
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  • Youjing Wang,

    1. Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
    2. The Key Laboratory of Living Donor Liver Transplantation, Ministry of Health, Nanjing, China
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  • Chen Chen,

    1. Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
    2. The Key Laboratory of Living Donor Liver Transplantation, Ministry of Health, Nanjing, China
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  • Lei Deng,

    1. Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
    2. The Key Laboratory of Living Donor Liver Transplantation, Ministry of Health, Nanjing, China
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  • Xingxu Huang,

    1. The State Key Laboratory of Pharmaceutical Biotechnology, Molecular Immunology and Cancer Research Center, School of Life Sciences, Nanjing University, Nanjing, China
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  • Xuehao Wang,

    1. Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
    2. The Key Laboratory of Living Donor Liver Transplantation, Ministry of Health, Nanjing, China
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  • Beicheng Sun

    Corresponding author
    1. Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, China
    2. The Key Laboratory of Living Donor Liver Transplantation, Ministry of Health, Nanjing, China
    • Liver Transplantation Center of the First Affiliated Hospital and State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing, Jiangsu Province, China
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    • fax: 86-25-86560946


  • Potential conflict of interest: Nothing to report.

  • This work was supported by grants from the National Natural Science Foundation (81072029 and 91029721; to B.S.), the National Basic Research Program of China (2012CB910800; to B.S.), and the New Century Excellent Talents in University, Ministry of Education (NCET-09-0160; to B.S.). The work was also supported, in part, by the Program for Development of Innovative Research Teams in the First Affiliated Hospital of Nanjing Medical University and the Priority Academic Program of Jiangsu Higher Education Institutions.

Abstract

Protein tyrosine phosphatase receptor type O (PTPRO), one of the receptor types of phosphotyrosine phosphatases (PTP), was recently described as a tumor suppressor in various kinds of cancers. We aimed to clarify the role of PTPRO in hepatocellular carcinoma (HCC). It was demonstrated in 180 pairs (120 male and 60 female) of clinical HCC specimens that the PTPRO level was significantly reduced, as compared with adjacent tissue, and the PTPRO level in male adjacent tissue was lower than in female. We further found that estrogen receptor alpha (ERα) could up-regulate PTPRO expression as a transcription factor. Moreover, an in vitro study showed that cell proliferation was inhibited and apoptosis was promoted in PTPRO-transduced HCC cell lines, whereas an in vivo study represented that tumor number and size was increased in ptpro−/− mice. As a result of its tumor-suppressive position, PTPRO was proved to down-regulate signal transducers and activators of transcription (STAT3) activity dependent on Janus kinase 2 (JAK2) and phosphoinositide 3-kinase (PI3K) dephosphorylation. Conclusions: PTPRO expression results in pathological deficiency and gender bias in HCC, which could be attributed to ERα regulation. The suppressive role of PTPRO in HCC could be ascribed to STAT3 inactivation. (HEPATOLOGY 2013)

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