Impact of Increased FUT8 Expression on the Extracellular Vesicle Proteome in Prostate Cancer Cells

Extracellular vesicles (EVs) are involved in intercellular communication, transporting proteins and nucleic acids to proximal and distal regions. There is evidence of glycosylation influencing protein routing into EVs; however, the impact of aberrant cellular glycotransferase expression on EV protein profiles has yet to be evaluated. In this study, we paired extracellular vesicle characterization and quantitative proteomics to determine the systemic impact of altered α(1,6)fucosyltranferase (FUT8) expression on prostate cancer-derived EVs. Our results showed that increased cellular expression of FUT8 could reduce the number of vesicles secreted by prostate cancer cells as well as increase the abundance of proteins associated with cell motility and prostate cancer metastasis. In addition, overexpression of FUT8 resulted in altered glycans on select EV-derived glycoproteins. This study presents the first evidence of altered cellular glycosylation impacting EV protein profiles and provides further rationale for exploring the functional role of glycosylation in EV biogenesis and biology.