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

B. Spangler, L. Vardimon, A. K. Bosserhoff, S. Kuphal

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)148-164
Number of pages17
JournalPigment Cell and Melanoma Research
Volume24
Issue number1
DOIs
StatePublished - Feb 2011

Keywords

  • C-Jun
  • Cytoskeleton
  • E-cadherin
  • Malignant melanoma
  • Post-transcriptional regulation

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