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“The role of ADK gene ín human melanoma cells

Grant number: 18/20665-0
Support type:Scholarships in Brazil - Master
Effective date (Start): March 01, 2019
Effective date (End): December 31, 2020
Field of knowledge:Biological Sciences - Genetics
Principal Investigator:Silvya Stuchi Maria-Engler
Grantee:Julia Rezende da Silva
Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:17/04926-6 - Melanoma and chemoresistance: in vitro and in silico models to exploit therapeutic targets, AP.TEM

Abstract

Melanoma is a malignant neoplasm that originates from melanocytes and represents a major public health problem. Although it accounts for only 3% of skin cancers, it is responsible for 80% of malignant neoplasms related to this organ. This is due to the fact that metastatic melanoma is refractory to conventional and targeted therapies and rapidly acquiring resistance to the specific inhibitors of mutated proteins in the MAPK pathway, such as BRAF. The group Skin Biology (FCF-USP) developed a screening in bioinformatics platforms using genomic databases to verify genes differentially expressed in nevi and metastatic melanomas - in which the adenosine kinase gene (ADK) was highlighted as a potential regulator of malignant transition. The ADK gene codes for a phosphotransferase enzyme that converts adenosine to adenosine monophosphate, so ADK regulates extracellular adenosine levels. Researches has shown an important relationship between adenosine and cell growth and proliferation, apoptosis, inflammation and immune system control, as well as angiogenesis. Since these factors are crucial for the development of tumor cells, several researchers have developed studies that relate adenosine levels, as well as ADK activity, to the progression of malignant tumors. Considering the search for effective targeted therapies for patients with melanoma, the investigation of ADK role in tumorigenesis may contribute to understand the mechanisms that cause the progression and resistance of melanoma, contributing to the development of an effective therapy. Therefore, the present study proposes to evaluate the expression of the ADK gene in susceptible and resistant human melanomas after treatment with vemurafenib (BRAF inhibitor), as well to study the impacts of genetic manipulation of this gene on proliferation, migration, invasion, apoptosis, cell cycle and metabolism.