Constitutive occurrence of E: N-cadherin heterodimers in adherens junctions of hepatocytes and derived tumors
Cell-cell junctions are pivotal for embryogenesis and tissue homeostasis but also play a major role in tumorigenesis, tumor invasion, and metastasis. E-cadherin (CDH1) and N-cadherin (CDH2) are two adherens junction’s transmembrane glycoproteins with tissue-specific expression patterns in epithelial...
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| Main Authors: | , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
12 August 2022
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| In: |
Cells
Year: 2022, Volume: 11, Issue: 16, Pages: 1-25 |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells11162507 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3390/cells11162507 Verlag, lizenzpflichtig, Volltext: https://www.mdpi.com/2073-4409/11/16/2507 
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| Author Notes: | Tiemo Sven Gerber, Dirk Andreas Ridder, Mario Schindeldecker, Arndt Weinmann, Diane Duret, Kai Breuhahn, Peter R. Galle, Peter Schirmacher, Wilfried Roth, Hauke Lang and Beate Katharina Straub |
| Summary: | Cell-cell junctions are pivotal for embryogenesis and tissue homeostasis but also play a major role in tumorigenesis, tumor invasion, and metastasis. E-cadherin (CDH1) and N-cadherin (CDH2) are two adherens junction’s transmembrane glycoproteins with tissue-specific expression patterns in epithelial and neural/mesenchymal cells. Aberrant expression has been implicated in the process of epithelial-mesenchymal transition (EMT) in malignant tumors. We could hitherto demonstrate cis-E:N-cadherin heterodimer in endoderm-derived cells. Using immunoprecipitation in cultured cells of the line PLC as well as in human hepatocellular carcinoma (HCC)-lysates, we isolated E-N-cadherin heterodimers in a complex with the plaque proteins α- and β-catenin, plakoglobin, and vinculin. In confocal laser scanning microscopy, E-cadherin co-localized with N-cadherin at the basolateral membrane of normal hepatocytes, hepatocellular adenoma (HCA), and in most cases of HCC. In addition, we analyzed E- and N-cadherin expression via immunohistochemistry in a large cohort of 868 HCCs from 570 patients, 25 HCA, and respective non-neoplastic liver tissue, and correlated our results with multiple prognostic markers. While E- or N-cadherin were similarly expressed in tumor sites with vascular invasion or HCC metastases, HCC with vascular encapsulated tumor clusters (VETC) displayed slightly reduced E-cadherin, and slightly increased N-cadherin expression. Analyzing The Cancer Genome Atlas patient cohort, we found that reduced mRNA levels of CDH1, but not CDH2 were significantly associated with unfavorable prognosis; however, in multivariate analysis, CDH1 did not correlate with prognosis. In summary, E- and N-cadherin are specific markers for hepatocytes and derived HCA and HCC. E:N-cadherin heterodimers are constitutively expressed in the hepatocytic lineage and only slightly altered in malignant progression, thereby not complying with the concept of EMT. |
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| Item Description: | Gesehen am 14.09.2022 |
| Physical Description: | Online Resource |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells11162507 |