ETS-1/RhoC signaling regulates the transcription factor c-Jun in melanoma

Barbara Spangler, Melanie Kappelmann, Birgit Schittek, Svenja Meierjohann, Lily Vardimon, Anja Katrin Bosserhoff*, Silke Kuphal

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Recently, we discovered that the loss of E-cadherin induces c-Jun protein expression, which is a member of the AP-1 transcription factor family and a key player in the processes of cell proliferation and tumor development and also found in elevated levels in melanomas. Notably, the mRNA level of c-Jun was not affected, suggesting that c-Jun is regulated at post-transcriptional level. Here, we present data that suggest that the dynamic cytoskeletal network, linked to E-cadherin, is involved in the regulation of the c-Jun protein and transcriptional activity. In a signaling cascade, the loss of E-cadherin activates the transcriptional regulator ETS-1 and consequently leads to the induction of RhoC expression that stabilizes c-Jun in melanoma. The link between RhoC and c-Jun seems to be indirect via the cytoskeleton. We conclude that the loss of E-cadherin mediated cell-adhesion induces c-Jun protein expression in a multistep process, offering several possibilities for therapeutic intervention.

Original languageEnglish
Pages (from-to)2801-2811
Number of pages11
JournalInternational Journal of Cancer
Volume130
Issue number12
DOIs
StatePublished - 15 Jun 2012

Keywords

  • ETS-1
  • Rho
  • c-Jun
  • cytoskeleton
  • melanoma

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