Dolores Di Vizio,
Professor,
Cedars Sinai Medical Center
Dr. Dolores Di Vizio is a pathologist and a molecular and cell biologist trained at Albert Einstein College of Medicine, and Harvard Medical School. Dr. Di Vizio holds an academic appointment as associate professor at Cedars-Sinai Medical Center, and at the University of California, Los Angeles. She is an Executive Chair of the International Society of Extracellular Vesicles (ISEV). Her group studies the molecular mechanisms of progression to advanced disease in human tumors, with a particular emphasis on large oncosomes, extracellular vesicles (EVs) shed into the extracellular space from fast migrating and metastatic amoeboid cancer cells. Her lab is currently profiling the large oncosomes and other EV populations by NGS and proteomics for functional and molecular characterization.
Palmitoyl-Proteomics to Identify Protein Signatures For Large and Small Cancer-derived Extracellular Vesicles in Patient Plasma
Tuesday, 18 February 2020 at 14:30
Add to Calendar ▼2020-02-18 14:30:002020-02-18 15:30:00Europe/LondonPalmitoyl-Proteomics to Identify Protein Signatures For Large and Small Cancer-derived Extracellular Vesicles in Patient PlasmaEV-based Diagnostics, Delivery and Therapeutics in Coronado Island, CaliforniaCoronado Island, CaliforniaSELECTBIOenquiries@selectbiosciences.com
Extracellular vesicles (EVs) are membrane-enclosed nano- and micro-particles that play an important role in cancer progression and have emerged as a promising source of circulating biomarkers. Historically called with various names, depending on the size, cargo, function and cellular and subcellular origin, they are currently categorized in large and small EVs. Our group and others have reported a cancer-specific population of EVs known as large oncosomes that is significantly larger than exosomes-like EVs, and is released by cancer cells during active metastatic migration. Protein S-acylation, also known as palmitoylation, has been proposed as a post-translational mechanism that modulates the dynamics of EV biogenesis and protein cargo sorting. However, technical challenges have limited large-scale profiling of the whole palmitoyl-proteins of EVs. We successfully employed a novel approach that combines low-background acyl-biotinyl exchange (LB-ABE) with label-free proteomics to analyze the palmitoyl proteome of large EVs (L-EVs) and small EVs (S-EVs) from prostate cancer cells and patient plasma. Here we report the first palmitoyl-protein signature of EVs, and demonstrate that L- and S-EVs harbor proteins associated with distinct biological processes and subcellular origin. We identified STEAP1, STEAP2, and ABBC4 as prostate cancer-specific palmitoyl proteins enriched in both EV populations in comparison with the originating cell lines. Importantly, the presence of the above proteins in EVs was significantly reduced upon inhibition of palmitoylation in the producing cells. We also performed additional experiments on a group of patients with metastatic prostate cancer and narrowed down a list of palmitoylated proteins that can be used as biomarkers in plasma. Finally, the palmitoyl-proteome of EVs in patient plasma significantly differed from the palmitoyl-proteome of whole plasma prior to purify EVs. These results suggest that palmitoylation may be involved in the differential sorting of proteins to distinct EV populations and allow for better detection of disease biomarkers.
Add to Calendar ▼2020-02-17 00:00:002020-02-18 00:00:00Europe/LondonEV-based Diagnostics, Delivery and TherapeuticsEV-based Diagnostics, Delivery and Therapeutics in Coronado Island, CaliforniaCoronado Island, CaliforniaSELECTBIOenquiries@selectbiosciences.com
Add to Calendar ▼2020-02-18 14:30:002020-02-18 15:30:00Europe/LondonPalmitoyl-Proteomics to Identify Protein Signatures For Large and Small Cancer-derived Extracellular Vesicles in Patient PlasmaEV-based Diagnostics, Delivery and Therapeutics in Coronado Island, CaliforniaCoronado Island, CaliforniaSELECTBIOenquiries@selectbiosciences.com
