WCCS/EADO 2016 | The importance of Wnt signalling in melanoma

Victoria Sherwood , PhD of the University of Dundee, Dundee, UK, talks about Wnt signalling at the 2016 World Congress on Cancers of the Skin (WCCS) and the Congress of the European Association of Dermato-Oncology (EADO) in Vienna, Austria. Dr Sherwood explains that Wnt signalling in melanoma has been studied for a number of years and an interesting link between Wnt signalling and metabolic regulation in melanoma cells has been found. Wnt signalling can be broadly divided into two distinct signalling subgroups – pathways that signal in a β-catenin dependent manner (canonical Wnt signaling pathway) and pathways that signal in a β-catenin independent manner (non-canonical Wnt signaling). It has been found that the non-canonical Wnt signaling pathway induces aerobic glycolysis in melanoma cells which can have an effect on promoting metastases in those tumors. However, the role of canonical Wnt signaling pathway is less understood. Some research suggests that the Wnt β-catenin pathway is poor for patient prognosis whilst other data suggests that it is actually good for patient outcome. Dr Sherwood explains that the controversy within the literature may potentially be due to context dependent effects within the tumors. Therefore, the metabolic regulation from the Wnt β-catenin signaling pathway in melanoma cells was looked at. It was found that there was a huge distinction between melanoma tumors that upregulated p10 and had high p10 expression, compared to tumor cells that had low p10 expression. She explains that in tumors with high p10 expression, when the Wnt β-catenin signaling pathway is activated, global cellular metabolism is suppressed. This has an effect on reducing metastases in various pre-clinical models. However, when looking at tumors that have low p10 expression, there was an opposite effect.