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Updated: May 31, 2026

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
ETS-1/RhoC signaling regulates the transcription factor c-Jun in melanoma
Barbara Spangler1, Melanie Kappelmann, Birgit Schittek
1Institute of Pathology, University of Regensburg, 93053 Regensburg, Germany.
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.
Insights
Loss of E-cadherin cell adhesion increases c-Jun protein, a key factor in melanoma development. This post-transcriptional regulation involves cytoskeletal changes and signaling pathways, offering therapeutic targets.
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Biology
Background:
- E-cadherin mediates cell-cell adhesion and its loss is linked to tumor progression.
- c-Jun (a member of the AP-1 transcription factor family) is crucial for cell proliferation and tumor development, with elevated levels in melanomas.
Purpose of the Study:
- To elucidate the post-transcriptional regulation of c-Jun protein expression following E-cadherin loss.
- To investigate the role of the cytoskeleton and specific signaling pathways in this process.
Main Methods:
- Analysis of c-Jun protein and mRNA levels in relation to E-cadherin expression.
- Investigation of the involvement of the cytoskeleton, ETS-1, and RhoC in the signaling cascade.
Main Results:
- Loss of E-cadherin induces c-Jun protein expression without affecting its mRNA levels, indicating post-transcriptional regulation.
- The dynamic cytoskeleton, linked to E-cadherin, regulates c-Jun protein and transcriptional activity.
- A signaling cascade involving ETS-1 and RhoC, indirectly via the cytoskeleton, stabilizes c-Jun in melanoma cells.
Conclusions:
- E-cadherin loss-mediated cell-adhesion induces c-Jun protein expression through a multistep process.
- The identified pathway involving the cytoskeleton, ETS-1, and RhoC presents potential therapeutic intervention points for melanoma.
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