Influence of the cytoplasmic domain of E-cadherin on endogenous N-cadherin expression in malignant melanoma

Kuphal, S and Bosserhoff, AK (2006) Influence of the cytoplasmic domain of E-cadherin on endogenous N-cadherin expression in malignant melanoma. ONCOGENE, 25 (2). pp. 248-259. ISSN 0950-9232, 1476-5594

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Abstract

E-cadherin is known to be an important molecule in epithelial-mesenchymal transition (EMT). Malignant transformation of melanocytes frequently attends with loss of E-cadherin expression and induction of expression of mesenchymal molecules like N-cadherin. The switch of the cadherin class is an interesting phenomenon of melanoma cells and in EMT in general. Therefore, we analysed the capacity of E-cadherin to regulate expression of N-cadherin in melanocytic cells. Our experiments revealed that melanoma cells downregulate endogenous N-cadherin expression after transient transfection of full-length E-cadherin, but also of the cytoplasmic domain of E-cadherin. Therefore, we concluded that the extracellular domain of E-cadherin and cell-cell contacts are not necessary for negative regulation of N-cadherin. Melanoma cells re-expressing full-length or cytoplasmatic E-cadherin have reduced NF kappa B activity in comparison to mock-transfected cells. Downregulation of NF kappa B activity, either directly or by re-expression of E-cadherin, led to a suppression of N-cadherin promoter activity and N-cadherin expression. Consequently, an NF kappa B-binding site in the N-cadherin promoter was characterized. In summary, our results suggest that N-cadherin is directly regulated by E-cadherin. Loss of E-cadherin induces NF kappa B activity and N-cadherin expression in tumorigenic EMT.

Item Type: Article
Uncontrolled Keywords: EPITHELIAL-MESENCHYMAL TRANSITION; CELL-ADHESION MOLECULE; UVOMORULIN-CATENIN COMPLEX; BREAST-CANCER CELLS; KAPPA-B; P-CADHERIN; TUMOR PROGRESSION; GASTRIC-CANCER; ALPHA-CATENIN; UP-REGULATION; E-cadherin; NF kappa B; N-cadherin regulation; cell contact
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Pathologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 03 Mar 2021 09:32
Last Modified: 03 Mar 2021 09:32
URI: https://pred.uni-regensburg.de/id/eprint/35247

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