title: ETS-1/RhoC signaling regulates the transcription factor c-Jun in melanoma.
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.
authors: Institute of Pathology, University of Regensburg, 93053 Regensburg, Germany.
authors: Barbara
authors: B
authors: Spangler
authors: Melanie
authors: M
authors: Kappelmann
authors: Birgit
authors: B
authors: Schittek
authors: Svenja
authors: S
authors: Meierjohann
authors: Lily
authors: L
authors: Vardimon
authors: Anja Katrin
authors: AK
authors: Bosserhoff
authors: Silke
authors: S
authors: Kuphal
mesh_terms: D015820:Cadherins / Q000378:metabolism; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000378:metabolism*; D015739:Nocodazole / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D050784:Proto-Oncogene Protein c-ets-1 / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D020741:rho GTP-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism*; D020742:rhoA GTP-Binding Protein / Q000096:biosynthesis; D020743:rhoB GTP-Binding Protein / Q000096:biosynthesis; D000075024:rhoC GTP-Binding Protein
chemical_list: D015820:Cadherins; C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D016755:Proto-Oncogene Proteins c-jun; D012333:RNA, Messenger; C066737:RHOA protein, human; C066690:RHOC protein, human; D020741:rho GTP-Binding Proteins; D020742:rhoA GTP-Binding Protein; D020743:rhoB GTP-Binding Protein; D000075024:rhoC GTP-Binding Protein; D015739:Nocodazole