Demonstration of a WNT5A-IL-6 positive feedback loop in melanoma cells : Dual interference of this loop more effectively impairs melanoma cell invasion
Författare
Summary, in English
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.
Avdelning/ar
- Experimentell cancerforskning, Malmö
- Experimentell patologi, Malmö
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
Publiceringsår
2016
Språk
Engelska
Sidor
37790-37802
Publikation/Tidskrift/Serie
Oncotarget
Volym
7
Issue
25
Dokumenttyp
Artikel i tidskrift
Förlag
Impact Journals
Ämne
- Basic Medicine
Nyckelord
- Anti-IL-6-Ab
- Box5
- Interleukin-6
- Melanoma invasion
- WNT5A
Status
Published
Forskningsgrupp
- Experimental Cancer Research, Malmö
- Experimental Pathology, Malmö
ISBN/ISSN/Övrigt
- ISSN: 1949-2553