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Investigation of the transcription factors inducing Epithelial-Mesenchymal Transition (EMT) in germ cells tumors

Grant number: 19/07502-8
Support type:Research Grants - Young Investigators Grants
Duration: April 01, 2021 - March 31, 2026
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal researcher:Mariana Tomazini Pinto
Grantee:Mariana Tomazini Pinto
Home Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil
Assoc. researchers:Adriane Feijó Evangelista ; Claudia de Oliveira Rodrigues ; Eduardo Caetano Albino da Silva ; Luiz Fernando Lopes ; Rui Manuel Vieira Reis ; Silvia Aparecida Teixeira

Abstract

Germ Cell Tumors (GCTs) are benign or malignant neoplasms derived from primordial germ cells that may occur at gonadal or extragonadal sites. The diagnosis of GCTs is performed with the analysis of tumor markers, which are also relevant in the prognosis and tumor response to chemotherapy. Another important prognostic factor is death due to cancer progression and metastasis, which can be controlled by the Epithelial-Mesenchymal Transition (EMT). In EMT the epithelial cells lose their characteristics and acquire mesenchymal phenotype. Several factors can induce EMT, including Snail and Slug transcription factors. The EMT was demonstrated in different tumor types, however, few studies evaluate the EMT in GCTs, the majority being carried out in adult patients, with a lack of information in pediatrics. Therefore, the aim of the present proposal is to evaluate the role of Snail and Slug transcription factors in the EMT induction in adult and pediatric patients with GCTs, in cell lines as well as in vivo models. First, an in silico analysis of EMT markers will be performed in adult patients with GCTs. The expression of EMT markers will also be evaluated in pediatric patients with GCTs using the NanoString platform and expression of Snail and Slug transcription factors will be assessed by immunohistochemistry. The effect of Snail and Slug overexpression and inhibition on EMT will be investigated in GCT lines. Finally, an in vivo model will be used to evaluate the role of Snail and Slug. Understanding the molecular mechanisms inducing EMT in GCTs will allow a better knowledge of cancer and metastasis, as well as contributing to the development of new therapeutic approaches. (AU)

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