Identification of novel mediators of age-associated chronic inflammation and cancer development through targeted proteomics

• Grant number: 17/50031-0
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2017
• End date: September 30, 2018
• Field of knowledge: Biological Sciences - Biochemistry - Chemistry of Macromolecules
• Agreement: University of Miami
• Mobility Program: SPRINT - Projetos de pesquisa - Mobilidade
• Principal Investigator: Vitor Marcel Faça
• Grantee: Vitor Marcel Faça
• Principal researcher abroad: Claudia Oliveira Rodrigues
• Institution abroad: University of Miami, United States
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated research grant: 16/03809-3 - Targeted proteomics of subcellular translocation during epithelial to mesenchymal transition (EMT), AP.R

Abstract

Cancer is a leading cause of death worldwide and aging ls considered one of the most important risk factors for cancer. Aging is characterized by chronic low-grade inflammation and oxidant damage, which lead to endothelial senescence and disruption of vascular function. Inflammatory mediators released from senescent endothelial cells contribute to cancer by promoting mutations in neighboring cells and resistance to apoptosis through induction of oncogenes, resulting in deregulated growth. The precise mechanisms that link age-associated chronic inflammation to cancer remain to be identified. Our goal is to investigate progressive molecular changes that occur during development of endothelial senescence-associated pro-inflammatory phenotype and identify potential regulators involved in inflammation and cancer during aging. The proto-oncogene c-Myc is ubiquitously expressed in different cell types and plays an important role in tissue homeostasis. Deregulated c-Myc expression is found in most types of cancer. Interestingly, preliminary findings on over expression of c-Myc specifically in mouse endothelial cells resolve age-associated inflammation and down-regulates cancer markers like Snail and Twist in a tissue-specific manner. The current proposal provides the unique opportunity to combine the expertise of Dr. Rodrigues in c-Myc and vascular inflammation and Dr. Faça in targeted proteomic to identify novel molecular regulators of age-associated inflammation specifically related to cancer. (AU)