Analysis of the role of TGF-² in drug resistance in germ cell tumors (GCTs) through regulating stem cell, apoptosis and epithelial-mesenchymal transition (EMT)

• Grant number: 18/13026-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): October 01, 2018
• Effective date (End): March 31, 2020
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Mariana Tomazini Pinto
• Grantee: Letícia Maria Barbosa Tufi
• Host Institution: Hospital do Câncer de Barretos. Fundação Pio XII (FP). Barretos , SP, Brazil

Abstract

Epithelial-mesenchymal transition (EMT) is a process in which epithelial cells lose their intercellular junctions and epithelial markers, acquire mesenchymal phenotype, as well as invasive and migratory properties. EMT is involved in several pathological conditions, including fibrosis, inflammation, and cancer development and metastasis. EMT has been demonstrated in several tumor types, however, few studies have evaluated EMT in germ cell tumors (GCTs). GCTs are neoplasms that can be classified as benign and malignant, derived from germ cells, arising from gonadal or extragonadal sites present in children, adolescents and adults. Some growth factors such as TGF-² as well as the transcription factors Snail, Slug, Zeb1/2, Twist are known to induce EMT. However, the molecular mechanisms involved in EMT induction in the GCTs have not been elucidated. Thus, the aim of this study is to evaluate the inducing factors of EMT in GCTs. Initially, an in silico analysis of the EMT markers on GCTs will be performed using the Oncomine and The Cancer Genome Atlas (TCGA) databases. Next, the EMT-inducing mechanisms that show differentiated expression in the in silico analysis will be evaluated in the GCTs cell lines by real-time PCR and Western blot analysis. Understanding the molecular mechanisms that induce EMTs in GCTs will allow a better understanding of cancer development and metastasis, as well as contribute to future therapeutic approaches.