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Demonstration of a WNT5A-IL-6 positive feedback loop in melanoma cells: Dual interference of this loop more effectively impairs melanoma cell invasion
Increased expression and signalling of WNT5A and interleukin-6 (IL-6) have both been shown to promote melanoma progression. Here, we investigated the proposed existence of a WNT5A-IL-6 positive feedback loop that drives melanoma migration and invasion. First, the HOPP algorithm revealed that the inv...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122349/ https://www.ncbi.nlm.nih.gov/pubmed/27191257 http://dx.doi.org/10.18632/oncotarget.9332 |
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author | Linnskog, Rickard Mohapatra, Purusottam Moradi, Farnaz Prasad, Chandra Prakash Andersson, Tommy |
author_facet | Linnskog, Rickard Mohapatra, Purusottam Moradi, Farnaz Prasad, Chandra Prakash Andersson, Tommy |
author_sort | Linnskog, Rickard |
collection | PubMed |
description | Increased expression and signalling of WNT5A and interleukin-6 (IL-6) have both been shown to promote melanoma progression. Here, we investigated the proposed existence of a WNT5A-IL-6 positive feedback loop that drives melanoma migration and invasion. First, the HOPP algorithm revealed that the invasive phenotype of cultured melanoma cells was significantly correlated with increased expression of WNT5A or IL-6. In three invasive melanoma cell lines, endogenous WNT5A protein expression was related to IL-6 protein secretion. Knockdown with anti-IL-6 siRNAs or treating WM852 melanoma cells with a neutralising anti-IL-6 antibody reduced WNT5A protein expression. Conversely, the silencing of WNT5A expression by WNT5A siRNAs or treating WM852 melanoma cells with Box5 (a WNT5A antagonist) significantly reduced IL-6 secretion. Interestingly, these effects occurred at the protein level but not at the transcriptional levels. Functionally, we demonstrated that combined siRNA knockdown of WNT5A and IL-6 expression or the simultaneous inhibition of WNT5A and IL-6 signalling inhibited melanoma cell invasion more effectively than suppressing each factor individually. Together, our results demonstrate that WNT5A and IL-6 are connected through a positive feedback loop in melanoma cells and that the combined targeting of both molecules could serve as an effective therapeutic means to reduce melanoma metastasis. |
format | Online Article Text |
id | pubmed-5122349 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-51223492016-12-05 Demonstration of a WNT5A-IL-6 positive feedback loop in melanoma cells: Dual interference of this loop more effectively impairs melanoma cell invasion Linnskog, Rickard Mohapatra, Purusottam Moradi, Farnaz Prasad, Chandra Prakash Andersson, Tommy Oncotarget Research Paper Increased expression and signalling of WNT5A and interleukin-6 (IL-6) have both been shown to promote melanoma progression. Here, we investigated the proposed existence of a WNT5A-IL-6 positive feedback loop that drives melanoma migration and invasion. First, the HOPP algorithm revealed that the invasive phenotype of cultured melanoma cells was significantly correlated with increased expression of WNT5A or IL-6. In three invasive melanoma cell lines, endogenous WNT5A protein expression was related to IL-6 protein secretion. Knockdown with anti-IL-6 siRNAs or treating WM852 melanoma cells with a neutralising anti-IL-6 antibody reduced WNT5A protein expression. Conversely, the silencing of WNT5A expression by WNT5A siRNAs or treating WM852 melanoma cells with Box5 (a WNT5A antagonist) significantly reduced IL-6 secretion. Interestingly, these effects occurred at the protein level but not at the transcriptional levels. Functionally, we demonstrated that combined siRNA knockdown of WNT5A and IL-6 expression or the simultaneous inhibition of WNT5A and IL-6 signalling inhibited melanoma cell invasion more effectively than suppressing each factor individually. Together, our results demonstrate that WNT5A and IL-6 are connected through a positive feedback loop in melanoma cells and that the combined targeting of both molecules could serve as an effective therapeutic means to reduce melanoma metastasis. Impact Journals LLC 2016-05-12 /pmc/articles/PMC5122349/ /pubmed/27191257 http://dx.doi.org/10.18632/oncotarget.9332 Text en Copyright: © 2016 Linnskog et al. http://creativecommons.org/licenses/by/2.5/ 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 credited. |
spellingShingle | Research Paper Linnskog, Rickard Mohapatra, Purusottam Moradi, Farnaz Prasad, Chandra Prakash Andersson, Tommy Demonstration of a WNT5A-IL-6 positive feedback loop in melanoma cells: Dual interference of this loop more effectively impairs melanoma cell invasion |
title | Demonstration of a WNT5A-IL-6 positive feedback loop in melanoma cells: Dual interference of this loop more effectively impairs melanoma cell invasion |
title_full | Demonstration of a WNT5A-IL-6 positive feedback loop in melanoma cells: Dual interference of this loop more effectively impairs melanoma cell invasion |
title_fullStr | Demonstration of a WNT5A-IL-6 positive feedback loop in melanoma cells: Dual interference of this loop more effectively impairs melanoma cell invasion |
title_full_unstemmed | Demonstration of a WNT5A-IL-6 positive feedback loop in melanoma cells: Dual interference of this loop more effectively impairs melanoma cell invasion |
title_short | Demonstration of a WNT5A-IL-6 positive feedback loop in melanoma cells: Dual interference of this loop more effectively impairs melanoma cell invasion |
title_sort | demonstration of a wnt5a-il-6 positive feedback loop in melanoma cells: dual interference of this loop more effectively impairs melanoma cell invasion |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5122349/ https://www.ncbi.nlm.nih.gov/pubmed/27191257 http://dx.doi.org/10.18632/oncotarget.9332 |
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