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

• Grant number: 19/07502-8
• Support Opportunities: Research Grants - Young Investigators Grants
• Start date: April 01, 2021
• End date: March 31, 2026
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Mariana Tomazini Pinto
• Grantee: Mariana Tomazini Pinto
• Host Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil
• Associated researchers: Adriane Feijó Evangelista ; Claudia de Oliveira Rodrigues ; Eduardo Caetano Albino da Silva ; Luiz Fernando Lopes ; Rui Manuel Vieira Reis ; Silvia Aparecida Teixeira
• Associated scholarship(s): 24/06770-7 - Evaluation of 5-azacitidine treatment in cisplatin-resistant germ cell tumor models, BP.DR; 24/06768-2 - DNA Methylation Profile in Pediatric Patients With Germ Cell Tumors, BP.MS; 23/07073-5 - Epithelial-mesenchymal transition: implications in pediatric patients with germ cell tumors, BP.MS; 22/16466-8 - Technical training in cellular and molecular biology., BP.TT; 22/07041-3 - Feasibility of nanopore sequencing for classification of pediatric germ cell tumors, BP.DD

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)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

PINTO, MARIANA TOMAZINI; MARTINS, GISELE EIRAS; VIEIRA, ANA GLENDA SANTAROSA; GALVAO, JANAINA MELLO SOARES; SOUZA, CRISTIANO DE PADUA; MACEDO, CARLA RENATA PACHECO DONATO; LOPES, LUIZ FERNANDO. Molecular Biology of Pediatric and Adult Ovarian Germ Cell Tumors: A Review. CANCERS, v. 15, n. 11, p. 23-pg., 2023-05-30. (19/07502-8)

VIEIRA, ANA GLENDA SANTAROSA; DA SILVA, LUCIANE SUSSUCHI; DA SILVA, EDUARDO CAETANO ALBINO; LAUS, ANA CAROLINA; FARIA, THAISSA MARIA VEIGA; LENGERT, ANDRE VAN HELVOORT; MARTINS, GISELE EIRAS; DE OLIVEIRA, MARCO ANTONIO; REIS, RUI MANUEL; LOPES, LUIZ FERNANDO; et al. Comprehensive microRNA expression analysis of pediatric gonadal germ cell tumors: unveiling novel biomarkers and signatures. MOLECULAR ONCOLOGY, v. 18, n. 6, p. 15-pg., 2024-05-09. (19/07502-8)

VITAL, PATRIK DA SILVA; BONATELLI, MURILO; DIAS, MARINA PEREIRA; DE SALIS, LARISSA VEDOVATO VILELA; PINTO, MARIANA TOMAZINI; BALTAZAR, FATIMA; MARIA-ENGLER, SILVYA STUCHI; PINHEIRO, CELINE. 3-Bromopyruvate Suppresses the Malignant Phenotype of Vemurafenib-Resistant Melanoma Cells. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v. 23, n. 24, p. 17-pg., 2022-12-01. (15/25351-6, 19/07502-8, 19/14189-4, 16/13021-4, 16/10821-0, 17/12620-4)