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Tumor Biology

, Volume 37, Issue 2, pp 2527–2535 | Cite as

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

  • Zheng Dang
  • Jianying Shangguan
  • Chao Zhang
  • Peng Hu
  • Yanshun Ren
  • Zhicheng Lv
  • Hongjun Xiang
  • Xianghui Wang
Original Article

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.

Keywords

Protocadherin-17 (PCDH-17) Hepatocellular carcinoma Metastasis ERK Prognosis 

Notes

Acknowledgments

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

Conflicts of interest

None

Supplementary material

13277_2015_3970_MOESM1_ESM.docx (13 kb)
Supplementary Table 1 The siRNA sequence of PCDH-17 (NM_001040429.2) (DOCX 13 kb)

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  • Zheng Dang
    • 1
  • Jianying Shangguan
    • 1
  • Chao Zhang
    • 1
  • Peng Hu
    • 1
  • Yanshun Ren
    • 1
  • Zhicheng Lv
    • 1
  • Hongjun Xiang
    • 1
  • Xianghui Wang
    • 1
  1. 1.The Department of Hepatobiliary SurgeryLanzhou General Hospital of People’s Liberation ArmyLanzhouPeople’s Republic of China

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