Proteomic study of epithelial to mesenchymal transition in breast cancer
| Grant number: | 12/09682-4 |
| Support type: | Scholarships in Brazil - Master |
| Effective date (Start): | August 01, 2012 |
| Effective date (End): | July 31, 2014 |
| Field of knowledge: | Biological Sciences - Biochemistry |
| Principal Investigator: | Vitor Marcel Faça |
| Grantee: | Camila de Souza Palma |
| Home Institution: | Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil |
| Associated research grant: | 11/09740-1 - Identification and validation of metastasis-related molecular signatures -In-Depth and targeted proteomic analysis of epithelial-mesenchymal transition in adenocarcinomas, AP.JP |
Abstract Breast cancer kills over 450 thousand people worldwide every year, and its metastasis is responsible for most of the deaths. Therefore, the most effective methods to decrease cancer morbidity and mortality consist in early detection, prevention and treatment of metastasis. Epithelial to mesenchymal transition (EMT) is a process that naturally occurs during embryogenesis and tissue repair and is also involved in cancer progression and metastasis. EMT induces complex cellular and microenviromental changes, such as decrease in cell-cell contact, resulting in loss of epithelial phenotype and acquisition of mesenchymal properties, which in turn promotes invasive and migratory capabilities to these cells. EMT can be triggered by several factors such as extracellular matrix components and growth factors, including TGF-², HGF e PDGF. Besides, overexpression of some transcription factors such as ZEB1, ZEB2, TWIST1, GSC, SNAIL, SLUG, FOXC1 and FOXC2 also induces EMT in vitro. Here, we aim to broaden the understanding of the complex molecular mechanisms of EMT modulated at the protein level, and for that we propose a detailed proteomic analysis of the breast adenocarcinoma cell lineage MDA-MB-231, induced to EMT by ZEB1 or TWIST1 overexpression. The protein components of the membrane, nucleus and cytoplasm will be quantitatively analyzed using the stable isotopic labeling of cells in culture (SILAC) method, fractionation of intact proteins and high-resolution mass spectrometry coupled with liquid chromatography (LC-MS/MS). With this detailed analysis we intend to identify proteins that are important to breast cancer progression and metastasis and that can possibly serve as targets for metastasis inhibition and/or disease diagnostics. | |