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ETS‐1/RhoC signaling regulates the transcription factor c‐Jun in melanoma
Author(s) -
Spangler Barbara,
Kappelmann Melanie,
Schittek Birgit,
Meierjohann Svenja,
Vardimon Lily,
Bosserhoff Anja Katrin,
Kuphal Silke
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.26277
Subject(s) - rhoc , transcription factor , regulator , c jun , microbiology and biotechnology , cadherin , transcriptional regulation , biology , transcription (linguistics) , signal transduction , cancer research , cell , gene , genetics , linguistics , philosophy , rhoa
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.