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Contribution of the interaction between Caveolin-1 and the enzyme GTP-cyclohydrolase along melanoma progression

Grant number: 17/13352-3
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): September 01, 2017
Effective date (End): August 31, 2018
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal Investigator:Fabiana Henriques Machado de Melo
Grantee:Heloísa Gabriel Tersariol
Home Institution: Faculdade de Ciências Médicas da Santa Casa de São Paulo (FCMSCSP). Fundação Arnaldo Vieira de Carvalho. São Paulo , SP, Brazil

Abstract

Cancer is one of the most important causes of death in the world. In Brazil, skin cancer corresponds about 25% of the diagnoses of this disease. Melanoma is one of the most lethal types of skin cancer, corresponding about 75% of deaths by cutaneous neoplasia. Reactive oxygen species (ROS) has been shown to have several roles in cancer cell development, such as activating pro-tumorigenic signalling pathways, enhancing cell survival and proliferation, and driving DNA damage and genetic instability. Previous data from our group has revealed that uncoupling nitric oxide synthase (NOS) contributes to increase superoxide anion levels and cell survival of SK-MEL-28, a human metastatic melanoma cell line, due decreased tetrahydrobiopterin (BH4) production, and here, we will apply this concept to our model of melanoma progression, that is composed of melanocytes, radial growth phase melanomas and vertical growth phase melanomas.BH4 is an essential cofactor of NOS and is synthetized either by the salvage pathway and by the de novo pathway. GTP cyclohydrolase-I is the limitant enzyme in the de novo synthesis pathway. The interaction between GTP cyclohydrolase-I and caveolin-1 decreases the activity of GTP cyclohydrolase-I and, in consequence, the production of tetrahydrobiopterin in endothelial cells. This work proposes the investigation of the possible interaction between GTP cyclohydrolase-I and caveolin-1 along melanoma progression and seeks to improve the knowledge of the physiopathology of the genesis of this neoplasia. (AU)