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Desmoglein 2 Depletion Leads to Increased Migration and Upregulation of the Chemoattractant Secretoneurin in Melanoma Cells

During development and progression of malignant melanoma, an important role has been attributed to alterations of cell-cell adhesions, in particular, to a “cadherin switch” from E- to N-cadherin. We have previously shown that a subtype of melanoma cells express the desmosomal cadherin desmoglein 2 a...

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Autores principales: Peitsch, Wiebke K., Doerflinger, Yvette, Fischer-Colbrie, Reiner, Huck, Volker, Bauer, Alexander T., Utikal, Jochen, Goerdt, Sergij, Schneider, Stefan W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3928442/
https://www.ncbi.nlm.nih.gov/pubmed/24558503
http://dx.doi.org/10.1371/journal.pone.0089491
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author Peitsch, Wiebke K.
Doerflinger, Yvette
Fischer-Colbrie, Reiner
Huck, Volker
Bauer, Alexander T.
Utikal, Jochen
Goerdt, Sergij
Schneider, Stefan W.
author_facet Peitsch, Wiebke K.
Doerflinger, Yvette
Fischer-Colbrie, Reiner
Huck, Volker
Bauer, Alexander T.
Utikal, Jochen
Goerdt, Sergij
Schneider, Stefan W.
author_sort Peitsch, Wiebke K.
collection PubMed
description During development and progression of malignant melanoma, an important role has been attributed to alterations of cell-cell adhesions, in particular, to a “cadherin switch” from E- to N-cadherin. We have previously shown that a subtype of melanoma cells express the desmosomal cadherin desmoglein 2 as non-junction-bound cell surface protein in addition to classical cadherins. To study the role of desmoglein 2 in melanoma cells, melanoma lines containing high endogenous amounts of desmoglein 2 were depleted of the protein by RNA interference. Transwell migration and scratch wounding assays showed markedly increased migration upon desmoglein 2 suppression whereas proliferation and viability remained unaltered. In gene expression profiles, desmoglein 2 depletion was associated with overexpression of migration-related genes. Strongest overexpression was found for secretogranin II which has not been reported in melanoma cells before. The bioactive peptide derived from secretogranin II, secretoneurin, is known to exert chemoattractive functions and was demonstrated here to stimulate melanoma cell migration. In summary, we show that desmoglein 2 expression attenuates migration of melanoma cells. The mechanism of desmoglein 2 impaired cell migration is mediated by downregulation of secretogranin II. Loss of desmoglein 2 increases expression of secretogranin II, followed by an enhanced migratory activity of melanoma cells. Our data add a new pathway of regulating melanoma cell migration related to a desmoglein 2 – secretogranin II axis.
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spelling pubmed-39284422014-02-20 Desmoglein 2 Depletion Leads to Increased Migration and Upregulation of the Chemoattractant Secretoneurin in Melanoma Cells Peitsch, Wiebke K. Doerflinger, Yvette Fischer-Colbrie, Reiner Huck, Volker Bauer, Alexander T. Utikal, Jochen Goerdt, Sergij Schneider, Stefan W. PLoS One Research Article During development and progression of malignant melanoma, an important role has been attributed to alterations of cell-cell adhesions, in particular, to a “cadherin switch” from E- to N-cadherin. We have previously shown that a subtype of melanoma cells express the desmosomal cadherin desmoglein 2 as non-junction-bound cell surface protein in addition to classical cadherins. To study the role of desmoglein 2 in melanoma cells, melanoma lines containing high endogenous amounts of desmoglein 2 were depleted of the protein by RNA interference. Transwell migration and scratch wounding assays showed markedly increased migration upon desmoglein 2 suppression whereas proliferation and viability remained unaltered. In gene expression profiles, desmoglein 2 depletion was associated with overexpression of migration-related genes. Strongest overexpression was found for secretogranin II which has not been reported in melanoma cells before. The bioactive peptide derived from secretogranin II, secretoneurin, is known to exert chemoattractive functions and was demonstrated here to stimulate melanoma cell migration. In summary, we show that desmoglein 2 expression attenuates migration of melanoma cells. The mechanism of desmoglein 2 impaired cell migration is mediated by downregulation of secretogranin II. Loss of desmoglein 2 increases expression of secretogranin II, followed by an enhanced migratory activity of melanoma cells. Our data add a new pathway of regulating melanoma cell migration related to a desmoglein 2 – secretogranin II axis. Public Library of Science 2014-02-18 /pmc/articles/PMC3928442/ /pubmed/24558503 http://dx.doi.org/10.1371/journal.pone.0089491 Text en © 2014 Peitsch et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Peitsch, Wiebke K.
Doerflinger, Yvette
Fischer-Colbrie, Reiner
Huck, Volker
Bauer, Alexander T.
Utikal, Jochen
Goerdt, Sergij
Schneider, Stefan W.
Desmoglein 2 Depletion Leads to Increased Migration and Upregulation of the Chemoattractant Secretoneurin in Melanoma Cells
title Desmoglein 2 Depletion Leads to Increased Migration and Upregulation of the Chemoattractant Secretoneurin in Melanoma Cells
title_full Desmoglein 2 Depletion Leads to Increased Migration and Upregulation of the Chemoattractant Secretoneurin in Melanoma Cells
title_fullStr Desmoglein 2 Depletion Leads to Increased Migration and Upregulation of the Chemoattractant Secretoneurin in Melanoma Cells
title_full_unstemmed Desmoglein 2 Depletion Leads to Increased Migration and Upregulation of the Chemoattractant Secretoneurin in Melanoma Cells
title_short Desmoglein 2 Depletion Leads to Increased Migration and Upregulation of the Chemoattractant Secretoneurin in Melanoma Cells
title_sort desmoglein 2 depletion leads to increased migration and upregulation of the chemoattractant secretoneurin in melanoma cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3928442/
https://www.ncbi.nlm.nih.gov/pubmed/24558503
http://dx.doi.org/10.1371/journal.pone.0089491
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