PXD017609

PXD017609 is an original dataset announced via ProteomeXchange.

Title	ErbB2 Site-Specific α2,6-Sialylation Regulates Gastric Cancer Cell Sensitivity to Trastuzumab
Description	The clinical performance of trastuzumab in the treatment of ErbB2-positive gastric cancer is severely hampered by the emergence of molecular resistance. The glycosylation landscape of ErbB2’s extracellular domain, and the molecular mechanisms through which it tunes gastric cell malignancy, including the acquisition of trastuzumab resistance, remain elusive. We show that the expression of ErbB2 sialylated glycoforms holds clinical utility in the prediction of clinical outcome and stratification of gastric cancer patients. In-depth glycoproteomic and glycomic analysis of ErbB2 extracellular region disclosed a site-specific profile in gastric cancer cells. We further demonstrate that ST6Gal1 sialyltransferase specifically targets ErbB2 N-glycosylation sites within the trastuzumab binding domain. Moreover, the abrogation of ST6Gal1-mediated α2,6-sialylation reshapes ErbB2 glycome and sensitizes gastric cancer cells to trastuzumab-induced cytotoxicity through receptor membrane stabilization and a downregulation of ErbB2 activation. Overall, this data demonstrates that aberrant sialylation tunes the molecular resistance of ErbB2-driven gastric cancer cells to trastuzumab.
HostingRepository	PRIDE
AnnounceDate	2021-05-12
AnnouncementXML	Submission_2021-05-11_22:40:27.233.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yassene Mohammed
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-02-19 01:42:08	ID requested
1	2021-05-11 07:08:55	announced
⏵ 2	2021-05-11 22:40:28	announced	2021-05-12: Updated project metadata.

Duarte HO, Rodrigues JG, Gomes C, Hensbergen PJ, Ederveen ALH, de Ru AH, Mereiter S, Pol, ó, nia A, Fernandes E, Ferreira JA, van Veelen PA, Santos LL, Wuhrer M, Gomes J, Reis CA, ST6Gal1 targets the ectodomain of ErbB2 in a site-specific manner and regulates gastric cancer cell sensitivity to trastuzumab. Oncogene, 40(21):3719-3733(2021) [pubmed]

10.1038/S41388-021-01801-W;

submitter keyword: Glycosylation,Glycoproteomics, Trastuzumab, Gastric Cancer

Celso A. Reis
contact affiliation	Institute for Research and Innovation in Health, University of Porto, Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto, Porto, Portugal; Institute for Biomedical Sciences Abel Salazar of the University of Porto, Porto, Portugal; Faculty of Medicine of the University of Porto, Porto, Portugal.
contact email	celsor@ipatimup.pt
lab head
Yassene Mohammed
contact affiliation	Leiden University Medcial Center
contact email	yassene@proteincentre.com
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/05/PXD017609

PRIDE project URI

• PRIDE
  1. PXD017609
     1. Label: PRIDE project
     2. Name: ErbB2 Site-Specific α2,6-Sialylation Regulates Gastric Cancer Cell Sensitivity to Trastuzumab