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dc.contributor.authorWeiß, N.*
dc.contributor.authorStegemann, A.*
dc.contributor.authorElsayed, Marwa A.T.A.*
dc.contributor.authorSchallreuter, Karin U.*
dc.contributor.authorLuger, T.A.*
dc.contributor.authorLoser, K.*
dc.contributor.authorMetze, D.*
dc.contributor.authorWeishaupt, C.*
dc.contributor.authorBöhm, M.*
dc.date.accessioned2015-01-27T11:50:30Z
dc.date.available2015-01-27T11:50:30Z
dc.date.issued2014
dc.identifier.citationWeiß N, Stegemann A, Elsayed MA, Schallreuter KU, Luger TA, Loser K, Metze D, Weishaupt C and Böhm M (2014) Journal of Investigative Dermatology. 134 (1):168-75.en_US
dc.identifier.urihttp://hdl.handle.net/10454/7065
dc.descriptionnoen_US
dc.description.abstractProhormone convertases (PCs) are endoproteases that process many substrates in addition to hormone precursors. Although overexpression of PCs is linked to carcinogenesis in some solid tumors, the role of subtilisin-kexin isoenzyme-1 (SKI-1) in this context is unknown. We show that SKI-1 is constitutively expressed in human pigment cells with higher SKI activity in seven out of eight melanoma cell lines compared with normal melanocytes. SKI-1 immunoreactivity is also detectable in tumor cells of melanoma metastases. Moreover, tissue samples of the latter display higher SKI-1 mRNA levels and activity than normal skin. From various stimuli tested, 12-O-tetradecanoylphorbol-13-acetate and tunicamycin affected SKI-1 expression. Importantly, SKI-1 inhibition by the cell-permeable enzyme inhibitor decanoyl-RRLL-chloromethylketone (dec-RRLL-CMK) not only suppressed proliferation and metabolic activity of melanoma cells in vitro but also reduced tumor growth of melanoma cells injected intracutaneously into immunodeficient mice. Mechanistic studies revealed that dec-RRLL-CMK induces classical apoptosis of melanoma cells in vitro and affects expression of several SKI-1 target genes including activating transcription factor 6 (ATF6). However, ATF6 gene silencing does not result in apoptosis of melanoma cells, suggesting that dec-RRLL-CMK induces cell death in an ATF6-independent manner. Our findings encourage further studies on SKI-1 as a potential target for melanoma therapy.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttp://dx.doi.org/10.1038/jid.2013.282en_US
dc.subjectProhormone convertases; PCs; Endoproteases; Apoptosis; Human melanoma cells; Melanoma therapyen_US
dc.titleInhibition of the prohormone convertase subtilisin-kexin isoenzyme-1 induces apoptosis in human melanoma cellsen_US
dc.status.refereedYesen_US
dc.typeArticleen_US
dc.type.versionNo full-text available in the repositoryen_US


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