STUDY OF THE ROLE OF ALPHA-SYNUCLEIN IN MELANOMA: exploring the relationship between cancer and neurodegeneration?

ZANOTTI, LUCÍA; MALIZIA, FLORENCIA; MENACHO MÁRQUEZ, MAURICIO

Congreso; PROTEIN MISFOLDING MEETING: crossroads between biology, cancer, and neurodegeneration; 2019

Both, cancer and Parkinson disease (PD), are a consequence of the interaction between genes and environmental factors. The key difference is that the biological processes leading to these pathologies occur in different cellular environments, leading to cell division or death.Recent studies suggested that alpha-synuclein (AS), one of the key regulators in PD, although toxic to dopaminergic neurons, is protective for advanced melanoma cells.In our work we began to explore the biological role of AS in tumoral cells derived from melanoma. First, by bioinformatic approaches we confirmed an increased expression of AS in melanoma samples. Indeed, we found that AS expression could have prognostic value for tumor patient outcome.In our melanoma models we identified that AS was expressed at considerably high levels and that part of AS is bound to membrane.By using shRNA technologies, we were able to modulate the levels of AS in mouse and human melanoma cells. Growth studies done with these cells indicated that reduced expression of AS leads to proliferative defects. Not only melanoma cell growth was affected by a decrease in AS levels; our preliminary data also indicate that reduced expression of AS leads to changes in actin cytoskeleton architecture and tubulin fibers organization. Interestingly, cells with reduced level of AS showed increased mitochondrial activity/number as observed by cytoplasmic formazan deposits.Altogether, our data indicate a putative role for AS in processes associated to melanoma growth and development.