Targeted proteomics of subcellular translocation during epithelial to mesenchymal ...
| Grant number: | 15/08693-0 |
| Support type: | Scholarships in Brazil - Doctorate |
| Effective date (Start): | September 01, 2015 |
| Effective date (End): | July 31, 2018 |
| 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 Subcellular localization of proteins and their trafficking between sub-compartments represent fundamental factors for their correct function. The aberrant localization of proteins contributes to the pathogenesis of several human diseases, including cancer. The association of cell fractionation methods and mass spectrometry based proteomic methods allow both the location and quantification of proteins in different sub-compartments as well as temporal dynamics measures and changes in their location in different cellular conditions. The correction of the location of disease-related proteins is, therefore, of great interest for therapeutic intervention and analysis of changes in protein localization in response to different stimuli is an important tool for the identification of cancer biomarkers, including breast cancer. Breast cancer is the most common type of cancer among women worldwide. Over one million new cases and 500 thousand deaths per year makes breast cancer the leading cause of death in women aged 40-59 years, and its metastasis is responsible for most deaths. Therefore, the most effective methods to decrease cancer morbidity and mortality consist in early detection, prevention and treatment of metastasis. A major challenge in the treatment of breast cancer is to identify reliable biomarkers to improve early diagnosis, screening, outcome prediction, therapeutic response, toxicity and identification of new therapeutic targets. In this context, we aim to assess changes in the subcellular localization of proteins in breast adenocarcinoma cell lines induced to epithelial-mesenchymal transition, a process that occurs naturally during embryogenesis and tissue repair, and is also involved in the progression and metastasis of cancer, serving as an in vitro model for the identification of proteins involved in cancer progression. For that, we will apply proteomics methods that combine subcellular fractionation and targeted mass spectrometry for a quantitative analysis of proteins involved in transport processes and translocation between sub-compartments. With this detailed analysis we intend to better understand the role of subcellular localization alteration in the regulation of biological process related to breast cancer and 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. | |