Evaluation of sepiapterin reductase role in melanoma development

• Grant number: 18/06923-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: July 01, 2018
• End date: June 30, 2019
• Field of knowledge: Biological Sciences - Morphology - Cytology and Cell Biology
• Principal Investigator: Fabiana Henriques Machado de Melo
• Grantee: Catarina Ji Yeun Kim
• Host Institution: Faculdade de Ciências Médicas da Santa Casa de São Paulo (FCMSCSP). Fundação Arnaldo Vieira de Carvalho. São Paulo , SP, Brazil

Abstract

The incidence of melanoma has been increasing in recent years due to augmented life expectancy and elevated exposure to ultraviolet rays. Melanoma is an extremely aggressive cancer, presenting a high rate of metastasis and consequently a high mortality rate. Late diagnosis, lack of tumor markers and inefficiency of available therapies are the main factors associated with high lethality. The high proliferative capacity of melanoma cells is correlated with alteration of numerous proteins, including growth factors, signaling proteins and cell cycle regulators. Among the altered cell cycle regulators are polyamines, aliphatic cations that play an important role in controlling proliferation, differentiation and apoptosis. The limiting enzyme in the synthesis of polyamines, ornithine decarboxylase, also presents altered expression and activity along the carcinogenesis, contributing to tumor progression. Recently, it has been shown that the interaction of ornithine decarboxylase with the enzyme sepiapterin reductase induces the synthesis of polyamines, contributing to the growth of neuroblastoma cells. Increased expression and activity of ornithine decarboxylase has been shown in melanoma cells, with consequent elevation in polyamine concentration. Data from our group showed increased expression of sepiapterin reductase in melanoma cell lines and its relation with shorter patient survival, however we do not know what the significance of this increase was for melanoma cells. Therefore, the aim of the study is to evaluate whether sepiapterin reductase regulates the activity of ornithine decarboxylase in melanomas, leading to polyamines production and consequently cell proliferation. (AU)