Project 3

1. Applicant

2. Topic

Regulation and role of c-Jun in malignant melanoma

3. Short summary

Transcription factors are essential regulators of gene expression. A deregulation of transcriptional activity which is often found during tumor development, changes several biological processes. The constitutive activity of the transcription factor superfamily AP-1 (hetero- or homodimers of c-Jun, c-Fos, JunB or further family members) influences the expression of a multitude of regulators of cell proliferation, migration and survival which are significantly involved in tumor development and metastasis. Although the relevance of AP-1 for cancerogenesis is known, molecular mechanisms for the regulation of constitutive activity in diverse tumors are largely unknown. Since previous data of our group could indicate that the inhibition of c-Jun leads to loss of the transcriptional activity of AP-1 in melanoma cells, c-Jun is essential for AP-1 activity in melanoma. Further experiments revealed that cell-cell contacts via E-cadherin have a negative impact on c-Jun expression in melanocytes. Concomitant with the loss of E-cadherin expression during melanoma development induction of c-Jun expression is acquired. Interestingly, we could further demonstrate that c-Jun is regulated by E-cadherin on post-transcriptional level. It seems that this adhesion dependent regulation is mainly influenced by cytoskeletal organization. Thus, the aim of this project is to clarify the molecular signaling mechanisms of E-cadherin dependent gene regulation and to determine the impact of c-Jun for melanoma development and progression.

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