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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

Linnskog, Rickard LU ; Mohapatra, Purusottam LU ; Moradi, Farnaz LU ; Prasad, Chandra Prakash LU and Andersson, Tommy LU (2016) In Oncotarget 7(25). p.37790-37802
Abstract

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... (More)

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.

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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Anti-IL-6-Ab, Box5, Interleukin-6, Melanoma invasion, WNT5A
in
Oncotarget
volume
7
issue
25
pages
13 pages
publisher
Impact Journals, LLC
external identifiers
  • Scopus:84978162105
ISSN
1949-2553
DOI
10.18632/oncotarget.9332
language
English
LU publication?
yes
id
2edef9b3-b618-4a74-9bf9-175cbad8b0fa
date added to LUP
2016-07-25 13:01:37
date last changed
2016-09-20 03:06:07
@misc{2edef9b3-b618-4a74-9bf9-175cbad8b0fa,
  abstract     = {<p>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.</p>},
  author       = {Linnskog, Rickard and Mohapatra, Purusottam and Moradi, Farnaz and Prasad, Chandra Prakash and Andersson, Tommy},
  issn         = {1949-2553},
  keyword      = {Anti-IL-6-Ab,Box5,Interleukin-6,Melanoma invasion,WNT5A},
  language     = {eng},
  number       = {25},
  pages        = {37790--37802},
  publisher    = {ARRAY(0x8c0bbc0)},
  series       = {Oncotarget},
  title        = {Demonstration of a WNT5A-IL-6 positive feedback loop in melanoma cells : Dual interference of this loop more effectively impairs melanoma cell invasion},
  url          = {http://dx.doi.org/10.18632/oncotarget.9332},
  volume       = {7},
  year         = {2016},
}