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

Int J Cancer. 2012 Jun 15;130(12):2801-11. doi: 10.1002/ijc.26277. Epub 2011 Aug 12.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cytoskeleton / metabolism
  • Humans
  • Melanoma / metabolism*
  • Nocodazole / pharmacology
  • Promoter Regions, Genetic
  • Proto-Oncogene Protein c-ets-1 / metabolism*
  • Proto-Oncogene Proteins c-jun / biosynthesis
  • Proto-Oncogene Proteins c-jun / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Signal Transduction / genetics
  • Transcription, Genetic
  • Transcriptional Activation
  • rho GTP-Binding Proteins / biosynthesis
  • rho GTP-Binding Proteins / metabolism*
  • rhoA GTP-Binding Protein / biosynthesis
  • rhoB GTP-Binding Protein / biosynthesis
  • rhoC GTP-Binding Protein


  • Cadherins
  • ETS1 protein, human
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Proteins c-jun
  • RNA, Messenger
  • RHOA protein, human
  • RHOC protein, human
  • rho GTP-Binding Proteins
  • rhoA GTP-Binding Protein
  • rhoB GTP-Binding Protein
  • rhoC GTP-Binding Protein
  • Nocodazole