PXD017039

PXD017039 is an original dataset announced via ProteomeXchange.

Title	Broad and thematic remodeling of the surface glycoproteome on isogenic cells tranformed with driving proliferative oncogenes
Description	The cell surface proteome, the surfaceome, is the interface for engaging the extracellular space in normal and cancer cells. Here we apply quantitative proteomics of N-linked glycoproteins to reveal how a collection of some 700 surface proteins is dramatically remodeled in an isogenic breast epithelial cell line stably expressing any of six of the most prominent proliferative oncogenes, including the receptor tyrosine kinases, EGFR and HER2, and downstream signaling partners such as KRAS, BRAF, MEK and AKT. We find that each oncogene has somewhat different surfaceomes but the functions of these proteins are harmonized by common biological themes including up-regulation of nutrient transporters, down-regulation of adhesion molecules and tumor suppressing phosphatases, and alteration in immune modulators. Addition of a potent MEK inhibitor that blocks MAPK signaling brings each oncogene-induced surfaceome back to a common state reflecting their strong dependence on the MAPK pathway to propagate signaling. Using a recently developed glyco-proteomics method of activated ion electron transfer dissociation (AI-ETD) we found massive oncogene-induced changes in 142 N-linked glycans and differential increases in complex hybrid glycans especially for KRAS and HER2 oncogenes. Overall, these studies provide a broad systems level view of how specific driver oncogenes remodel the surface glycoproteome in a cell autologous fashion, and suggest possible surface targets, and combinations thereof, for drug and biomarker discovery.
HostingRepository	PRIDE
AnnounceDate	2020-04-08
AnnouncementXML	Submission_2020-04-07_22:43:15.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Gary Wilson
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; complex glycosylation; iodoacetamide derivatized residue; deamidated residue
Instrument	Orbitrap Fusion Lumos; Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2020-01-09 08:34:17	ID requested
⏵ 1	2020-04-07 22:43:16	announced

Leung KK, Wilson GM, Kirkemo LL, Riley NM, Coon JJ, Wells JA, Broad and thematic remodeling of the surfaceome and glycoproteome on isogenic cells transformed with driving proliferative oncogenes. Proc Natl Acad Sci U S A, 117(14):7764-7775(2020) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: Oncogenes, Glycoproteomics, Surfaceome, MAPK signaling pathway

James Wells
contact affiliation	Department of Pharmaceutical Chemistry, University of California - San Francisco
contact email	jim.wells@ucsf.edu
lab head
Gary Wilson
contact affiliation	UW-Madison
contact email	gwilson9@wisc.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD017039
     1. Label: PRIDE project
     2. Name: Broad and thematic remodeling of the surface glycoproteome on isogenic cells tranformed with driving proliferative oncogenes