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Loss of protocadherin-17 (PCDH-17) promotes metastasis and invasion through hyperactivation of EGFR/MEK/ERK signaling pathway in hepatocellular carcinoma

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Tumor Biology

Abstract

Metastasis has been one of the major reasons for cancer-related mortality, with multiple genes and pathways being involved in this complex process. Given the molecular variations underlying metastasis of hepatocellular carcinoma (HCC) remains largely unknown; in our previous work, we found copying number of protocadherin-17 (PCDH-17) was significantly deleted in HCC tissues that occurred to metastasize compared with that in the primary HCC without metastasis. Therefore, we hypothesized that PCDH-17 may suppress the metastasis of HCC. There has been, however, no relevant literature available regarding PCDH-17 in HCC. In the present study, we have immunohistochemically detected and clinicopathologically analyzed the expression of PCDH-17 in vivo in clinical tissues; besides, we have explored the role of PCDH-17 ex vivo using a panel of HCC cell lines. It was discovered that PCDH-17 expression was clinically correlated with overall prognosis as well as metastasis in vivo and that PCDH-17 inhibited metastasis via EGFR/MEK/ERK signaling pathway ex vivo. Together, our results obtained both in vivo and ex vivo suggested that activation of EGFR/MEK/ERK signaling pathway through PCDH-17 promotes metastasis in HCC.

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Acknowledgments

The work was supported by the Department of Hepatobiliary Surgery, Lanzhou General Hospital of People’s Liberation Army.

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    Authors and Affiliations

    1. The Department of Hepatobiliary Surgery, Lanzhou General Hospital of People’s Liberation Army, Lanzhou, Gansu, 730050, People’s Republic of China

      Zheng Dang, Jianying Shangguan, Chao Zhang, Peng Hu, Yanshun Ren, Zhicheng Lv, Hongjun Xiang & Xianghui Wang

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    1. Zheng Dang
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    2. Jianying Shangguan
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    3. Chao Zhang
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    4. Peng Hu
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    7. Hongjun Xiang
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    8. Xianghui Wang
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    Corresponding authors

    Correspondence to Hongjun Xiang or Xianghui Wang.

    Additional information

    Zheng Dang, Jianying Shangguan and Chao Zhang contributed equally to this work.

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    Supplementary Table 1

    The siRNA sequence of PCDH-17 (NM_001040429.2) (DOCX 13 kb)

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    Dang, Z., Shangguan, J., Zhang, C. et al. Loss of protocadherin-17 (PCDH-17) promotes metastasis and invasion through hyperactivation of EGFR/MEK/ERK signaling pathway in hepatocellular carcinoma. Tumor Biol. 37, 2527–2535 (2016). https://doi.org/10.1007/s13277-015-3970-5

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    • DOI: https://doi.org/10.1007/s13277-015-3970-5

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