Post-transcriptional regulation controlled by E-cadherin is important for c-Jun activity in melanoma

• Published in: Pigment cell and melanoma research Vol. 24; no. 1; pp. 148 - 164
• Main Authors: Spangler, B., Vardimon, L., Bosserhoff, A. K., Kuphal, S.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-02-2011
• Subjects: c-Jun; c-Jun protein; Cadherins - metabolism; Cell Adhesion; Cell Line, Tumor; Cytoskeleton; Cytoskeleton - metabolism; Data processing; E-Cadherin; Gene Expression Regulation, Neoplastic; Humans; malignant melanoma; Melanocytes; Melanoma; Melanoma - enzymology; Melanoma - genetics; Melanoma - pathology; Mitogen-Activated Protein Kinases - metabolism; Pigments; Post-transcription; post-transcriptional regulation; Proto-Oncogene Proteins c-jun - genetics; Proto-Oncogene Proteins c-jun - metabolism; Proto-oncogenes; Signal transduction; Transcription; Transcription factors; Transcription, Genetic; Translation; Tumorigenesis
• ISSN: 1755-1471; 1755-148X
• DOI: 10.1111/j.1755-148X.2010.00787.x

Summary
A central event in the development of malignant melanoma is the loss of the tumor‐suppressor protein E‐cadherin. Here, we report that this loss is linked to the activation of the proto‐oncogene c‐Jun, a key player in tumorigenesis. In vivo, malignant melanomas show strong expression of the c‐Jun protein in contrast to melanocytes. Interestingly, c‐Jun mRNA levels did not differ in the melanoma cell lines when compared to melanocytes, suggesting that c‐Jun could be regulated at the post‐transcriptional level. To uncover the link between E‐cadherin and c‐Jun, we re‐expressed E‐cadherin in melanoma cells and detected decreased protein expression and activity of c‐Jun. Furthermore, c‐Jun accumulation is dependent on active E‐cadherin‐mediated cell–cell adhesion and regulated via the cytoskeleton. Additionally, we determined that, with respect to c‐Jun regulation, there are two melanoma subgroups. One subgroup regulates c‐Jun expression via the newly discovered E‐cadherin‐dependent signaling pathway, whereas the other subgroup uses the MAPKinases to regulate its expression. In summary, our data provide novel insights into the tumor‐suppressor function of E‐cadherin, which contributes to the suppression of c‐Jun protein translation and transcriptional activity independent of MAPKinases.