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

Tumour Biol. 2016 Feb;37(2):2527-35. doi: 10.1007/s13277-015-3970-5. Epub 2015 Sep 19.

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: ERK; Hepatocellular carcinoma; Metastasis; Prognosis; Protocadherin-17 (PCDH-17).

MeSH terms

  • Animals
  • Cadherins / genetics*
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics*
  • ErbB Receptors / genetics*
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology
  • MAP Kinase Signaling System / genetics*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Metastasis / genetics*
  • Neoplasm Metastasis / pathology
  • Prognosis
  • Signal Transduction / genetics

Substances

  • Cadherins
  • PCDH17 protein, human
  • EGFR protein, human
  • ErbB Receptors