Comprehensive palmitoyl‐proteomic analysis identifies distinct protein signatures for large and small cancer‐derived extracellular vesicles. Issue 1 (10th June 2020)

• Record Type: Journal Article
• Authors: Mariscal, Javier; Vagner, Tatyana; Kim, Minhyung; Zhou, Bo; Chin, Andrew; Zandian, Mandana; Freeman, Michael R.; You, Sungyong; Zijlstra, Andries; Yang, Wei; Di Vizio, Dolores
• Is Part Of: Journal of extracellular vesicles. Volume 9:Issue 1(2020)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-06-10
• Subjects: Palmitoylation -- S‐acylation -- extracellular vesicles -- palmitoyl‐proteomics -- prostate cancer -- large oncosomes -- exosomes; Cells -- Mechanical properties -- Periodicals; Transport Vesicles; Cells -- Mechanical properties; Periodicals; Fulltext; Internet Resources; Periodicals; Electronic journals; Periodicals; 571.63
• DOI: 10.1080/20013078.2020.1764192
• Languages: English
• ISSNs: 2001-3078

Abstract

ABSTRACT: Extracellular vesicles (EVs) are membrane‐enclosed particles that play an important role in cancer progression and have emerged as a promising source of circulating biomarkers. Protein S ‐acylation, frequently called 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 analyse the palmitoyl‐proteome of large EVs (L‐EVs) and small EVs (S‐EVs) from prostate cancer cells. Here we report the first palmitoyl‐protein signature of EVs, and demonstrate that L‐ and S‐EVs harbour proteins associated with distinct biological processes and subcellular origin. We identified STEAP1, STEAP2, and ABCC4 as prostate cancer‐specific palmitoyl‐proteins abundant in both EV populations. Importantly, localization of the above proteins in EVs was reduced upon inhibition of palmitoylation in the producing cells. Our results suggest that this post‐translational modification may play a role in the sorting of the EV‐bound secretome and possibly enable selective detection of disease biomarkers.