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Identification of important targets associated with stem-like state and epithelial mesenchymal transition along melanocyte malignant transformation

Grant number: 14/01168-5
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): May 01, 2014
Effective date (End): April 30, 2015
Field of knowledge:Biological Sciences - Biochemistry
Principal Investigator:Miriam Galvonas Jasiulionis
Grantee:Alice Santana Morais
Supervisor abroad: Meenhard Herlyn
Home Institution: Escola Paulista de Medicina (EPM). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil
Local de pesquisa : Wistar Institute, United States  
Associated to the scholarship:11/18959-7 - Research in the early stages of melanoma genesis of key regulators of epithelial-mesenchymal transition and stem cell-like phenotype epigenetically controlled, BP.DR

Abstract

Melanoma is an aggressive form of skin cancer that is responsible for the vast majority of skin cancer deaths and its incidence continues to increase worldwide. It is known the existence of many factors that contribute to melanoma development and to increase its incidence, however, there are many questions to be elucidated about the genetics, epigenetics and metabolomics changes that occur as adaptation of melanocytes to the microenvironment during transformation. Although melanoma is highly curable when early diagnosed, the metastatic melanoma detains the worst prognosis and remains one of the most resistant cancers to treatment. The unsuccessful of current approach treatments can be a result of poorly understood cancer cell population heterogeneity and the influence of microenvironment on this population. In this light, continuous efforts are made to comprehend the presence of cancer stem cells (CSC) in these subpopulations and their participation on metastatic disease, acquisition of resistance to therapy and possible recurrences. Based on a model of melanocyte malignant transformation which represents distinct phases of melanoma genesis and is related with sustained stress conditions, our laboratory found evidences of a transient change from epithelial to mesenchymal phenotype, mainly in intermediate stages of progression, along malignant transformation. In addition, we observed, in these same phases, increased expression of genes associated with the acquisition of stem-cell phenotype and chromatin remodelling. The aim of this project is to investigate targets associated with stem cell-like state and epithelial-to-mesenchymal transition that are important to melanocyte malignant transformation. With technologies and knowhow about melanocyte reprogramming and melanoma from Meenhard Herlyn's laboratory, we can become aware of information to understand the relationship between heterogeneous subpopulations, cellular microenvironment and the establishment and progression of a tumor, observed in our model. Besides improving the understanding of this pathology, selected targets could be assessed, in future, as potential prognostic agents or therapeutic targets. (AU)