Paired basic amino acid-cleaving enzyme 4 (PCSK6): An emerging new target molecule in human melanoma

Carsten Weishaupt, Arianna Mastrofrancesco, Dieter Metze, Björn Kemper, Agatha Stegemann, Mauro Picardo, Andres J.P. Klein-Szanto, Markus Böhm

Research output: Contribution to journalArticlepeer-review

Abstract

Although recent therapeutic developments raise hope, melanoma remains a devastating disease with a need for new treatment targets. In other tumours prohormone convertases have been shown to be pro-tumourigenic as they are involved in processing preforms of matrix-metalloproteinases, growth factors and adhesion molecules. The aim of this study was to look for new treatment options for melanoma, by investigating the role of the prohormone convertase Paired basic Amino acid-Cleaving Enzyme 4 (PACE4/PCSK6) in melanoma cell lines and human melanoma tissue. PACE4-transfected A375 melanoma cells displayed significantly increased proliferation, MMP-2 production, gelatinase activity and migratory capacity in vitro compared with sham-transfected cells. In vivo, elevated PACE4 expression resulted in significantly increased tumour growth on immunodeficient mice. In the majority of 45ctaDV human primary melanomas and melanoma metastases ex vivo PACE4 immunoreactivity was detectable, while it was absent in in situ melanomas. These results indicate PACE4 as a regulator of melanoma cell aggressiveness.

Original languageEnglish
Article numberadv00157
Pages (from-to)1-9
Number of pages9
JournalActa Dermato-Venereologica
Volume100
Issue number10
DOIs
Publication statusPublished - May 2020

Keywords

  • Carcinogenesis
  • Melanocytes
  • Melanoma
  • PACE4
  • PCSK6
  • Prohormone convertases

ASJC Scopus subject areas

  • Dermatology

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