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

David J. Clark; Michael Schnaubelt; Naseruddin Hoti; Yingwei Hu; Yangying Zhou; Mahta Gooya; Hui Zhang

doi:10.1021/acs.jproteome.9b00578

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

David J. Clark, Michael Schnaubelt, Naseruddin Hoti, Yingwei Hu, Yangying Zhou, Mahta Gooya, Hui Zhang

School of Medicine

Research output: Contribution to journal › Article › peer-review

7 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	2195-2205
Number of pages	11
Journal	Journal of proteome research
Volume	19
Issue number	6
DOIs	https://doi.org/10.1021/acs.jproteome.9b00578
State	Published - Jun 5 2020

Keywords

core fucosylation
extracellular vesicles
glycoproteins
prostate cancer
proteomics

ASJC Scopus subject areas

Chemistry(all)
Biochemistry

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10.1021/acs.jproteome.9b00578

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title = "Impact of Increased FUT8 Expression on the Extracellular Vesicle Proteome in Prostate Cancer Cells",

abstract = "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.",

keywords = "core fucosylation, extracellular vesicles, glycoproteins, prostate cancer, proteomics",

author = "Clark, {David J.} and Michael Schnaubelt and Naseruddin Hoti and Yingwei Hu and Yangying Zhou and Mahta Gooya and Hui Zhang",

note = "Funding Information: This work was supported by the National Institutes of Health, National Cancer Institute, the Early Detection Research Network (EDRN, U01CA152813), and the Clinical Proteomic Tumor Analysis Consortium (CPTAC, U24CA210985). Electron microscopy services reported in this publication were performed at The Johns Hopkins University School of Medicine Microscope Facility supported by the National Center for Research Resources of the National Institutes of Health under award number S10RR026445. Publisher Copyright: Copyright {\textcopyright} 2020 American Chemical Society.",

year = "2020",

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doi = "10.1021/acs.jproteome.9b00578",

language = "English (US)",

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AU - Clark, David J.

AU - Schnaubelt, Michael

AU - Hoti, Naseruddin

AU - Hu, Yingwei

AU - Zhou, Yangying

AU - Gooya, Mahta

AU - Zhang, Hui

N1 - Funding Information: This work was supported by the National Institutes of Health, National Cancer Institute, the Early Detection Research Network (EDRN, U01CA152813), and the Clinical Proteomic Tumor Analysis Consortium (CPTAC, U24CA210985). Electron microscopy services reported in this publication were performed at The Johns Hopkins University School of Medicine Microscope Facility supported by the National Center for Research Resources of the National Institutes of Health under award number S10RR026445. Publisher Copyright: Copyright © 2020 American Chemical Society.

PY - 2020/6/5

Y1 - 2020/6/5

N2 - 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.

AB - 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.

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

Abstract

Keywords

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