PMID- 27095597
OWN - NLM
STAT- MEDLINE
DCOM- 20171120
LR  - 20240326
IS  - 1876-7737 (Electronic)
IS  - 1874-3919 (Print)
IS  - 1874-3919 (Linking)
VI  - 145
DP  - 2016 Aug 11
TI  - A metabolic labeling approach for glycoproteomic analysis reveals altered 
      glycoprotein expression upon GALNT3 knockdown in ovarian cancer cells.
PG  - 91-102
LID - S1874-3919(16)30130-0 [pii]
LID - 10.1016/j.jprot.2016.04.009 [doi]
AB  - Epithelial ovarian cancer (EOC) is a disease responsible for more deaths among 
      women in the Western world than all other gynecologic malignancies. There is 
      urgent need for new therapeutic targets and a better understanding of EOC 
      initiation and progression. We have previously identified the polypeptide 
      N-acetylgalactosaminyltransferase 3 (GALNT3) gene, a member of the 
      GalNAc-transferases (GalNAc-Ts) gene family, as hypomethylated and overexpressed 
      in high-grade serous EOC tumors, compared to low malignant potential EOC tumors 
      and normal ovarian tissues. This data also suggested for a role of GALNT3 in 
      aberrant EOC glycosylation, possibly implicated in disease progression. To 
      evaluate differential glycosylation in EOC caused by modulations in GALNT3 
      expression, we used a metabolic labeling strategy for enrichment and mass 
      spectrometry-based characterization of glycoproteins following GALNT3 gene 
      knockdown (KD) in A2780s EOC cells. A total of 589 differentially expressed 
      glycoproteins were identified upon GALNT3 KD. Most identified proteins were 
      involved in mechanisms of cellular metabolic functions, post-translational 
      modifications, and some have been reported to be implicated in EOC etiology. The 
      GALNT3-dependent glycoproteins identified by this metabolic labeling approach 
      support the oncogenic role of GALNT3 in EOC dissemination and may be pursued as 
      novel EOC biomarkers and/or therapeutic targets. BIOLOGICAL SIGNIFICANCE: 
      Knowledge of the O-glycoproteome has been relatively elusive, and the functions 
      of the individual polypeptide GalNAc-Ts have been poorly characterized. 
      Alterations in GalNAc-Ts expression were shown to provide huge variability in the 
      O-glycoproteome in various pathologies, including cancer. The application of a 
      chemical biology approach for the metabolic labeling and subsequent 
      characterization of O-glycoproteins in EOC using the Ac4GalNAz metabolite has 
      provided a strategy allowing for proteomic discovery of GalNAc-Ts specific 
      functions. Our study supports an essential role of one of the GalNAc-Ts - GALNT3, 
      in EOC dissemination, including its implication in modulating PTMs and EOC 
      metabolism. Our approach validates the use of the applied metabolic strategy to 
      identify important functions of GalNAc-Ts in normal and pathological conditions.
CI  - Copyright (c) 2016 Elsevier B.V. All rights reserved.
FAU - Sheta, Razan
AU  - Sheta R
AD  - Department of Molecular Medicine, Laval University, Quebec, PQ, Canada; Centre de 
      recherche du CHU de Quebec, L'Hotel-Dieu de Quebec, Quebec, PQ, Canada.
FAU - Woo, Christina M
AU  - Woo CM
AD  - Department of Chemistry, Stanford University, Stanford, CA, USA.
FAU - Roux-Dalvai, Florence
AU  - Roux-Dalvai F
AD  - Centre de recherche du CHU de Quebec, CHUL, Quebec, PQ, Canada.
FAU - Fournier, Frederic
AU  - Fournier F
AD  - Centre de recherche du CHU de Quebec, CHUL, Quebec, PQ, Canada.
FAU - Bourassa, Sylvie
AU  - Bourassa S
AD  - Centre de recherche du CHU de Quebec, CHUL, Quebec, PQ, Canada.
FAU - Droit, Arnaud
AU  - Droit A
AD  - Department of Molecular Medicine, Laval University, Quebec, PQ, Canada; Centre de 
      recherche du CHU de Quebec, CHUL, Quebec, PQ, Canada.
FAU - Bertozzi, Carolyn R
AU  - Bertozzi CR
AD  - Department of Chemistry, Stanford University, Stanford, CA, USA; Howard Hughes 
      Medical Institute, Stanford University, Stanford, CA, USA.
FAU - Bachvarov, Dimcho
AU  - Bachvarov D
AD  - Department of Molecular Medicine, Laval University, Quebec, PQ, Canada; Centre de 
      recherche du CHU de Quebec, L'Hotel-Dieu de Quebec, Quebec, PQ, Canada.
LA  - eng
GR  - HHMI/Howard Hughes Medical Institute/United States
GR  - R01 CA200423/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20160417
PL  - Netherlands
TA  - J Proteomics
JT  - Journal of proteomics
JID - 101475056
RN  - 0 (Glycoproteins)
RN  - EC 2.4.1.- (N-Acetylgalactosaminyltransferases)
SB  - IM
MH  - Female
MH  - *Gene Expression Profiling
MH  - Gene Knockdown Techniques
MH  - Glycoproteins/*analysis/genetics
MH  - Glycosylation
MH  - Humans
MH  - N-Acetylgalactosaminyltransferases/*genetics
MH  - Ovarian Neoplasms/chemistry/*genetics/metabolism
MH  - Proteomics/*methods
MH  - Polypeptide N-acetylgalactosaminyltransferase
PMC - PMC5436706
MID - NIHMS855913
OTO - NOTNLM
OT  - Epithelial ovarian cancer
OT  - GALNT3
OT  - Glycoproteomics
OT  - Glycosylation
OT  - Metabolic labeling
OT  - Pathway and network analysis
COIS- Conflict of interest The authors declare no conflicts of interest.
EDAT- 2016/04/21 06:00
MHDA- 2017/11/29 06:00
PMCR- 2017/08/11
CRDT- 2016/04/21 06:00
PHST- 2016/02/05 00:00 [received]
PHST- 2016/03/31 00:00 [revised]
PHST- 2016/04/12 00:00 [accepted]
PHST- 2016/04/21 06:00 [entrez]
PHST- 2016/04/21 06:00 [pubmed]
PHST- 2017/11/29 06:00 [medline]
PHST- 2017/08/11 00:00 [pmc-release]
AID - S1874-3919(16)30130-0 [pii]
AID - 10.1016/j.jprot.2016.04.009 [doi]
PST - ppublish
SO  - J Proteomics. 2016 Aug 11;145:91-102. doi: 10.1016/j.jprot.2016.04.009. Epub 2016 
      Apr 17.