PXD022240

PXD022240 is an original dataset announced via ProteomeXchange.

Title	Widespread multi-targeted therapy resistance via drug-induced secretome fucosylation
Description	Cancer secretome is a reservoir for aberrant glycosylation. How therapies alter this post translational cancer hallmark and the consequences thereof remain elusive. Here we show that an elevated secretome fucosylation is a pan-cancer signature of both response and resistance to multiple targeted therapies. Large-scale pharmacogenomics revealed that fucosylation genes display widespread association with resistance to these therapies. In both cancer cell cultures and patients, targeted kinase inhibitors distinctively induced core fucosylation of secreted proteins less than 60 kDa. Label-free proteomics of N-glycomes revealed that fucosylation of the antioxidant PON1 is a critical component of the therapy induced secretome. Core fucosylation in the Golgi impacts PON1 stability and folding prior to secretion, promoting a more degradation-resistant PON1. Non-specific and PON1-specific secretome deglycosylation both limited the expansion of resistant clones in a tumor regression model. Our findings demonstrate that core fucosylation is a common modification indirectly induced by targeted therapies that paradoxically promotes resistance
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:51:16.133.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD022240
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Pavel Sinitcyn
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2020-10-29 02:40:15	ID requested
1	2023-04-05 08:43:22	announced
⏵ 2	2023-11-14 08:51:16	announced	2023-11-14: Updated project metadata.

10.6019/PXD022240;

submitter keyword: n-linked glycosylation, resistance,fucosylation, targeted therapy, secretome

Prof. Yoosik Kim
contact affiliation	Korea Advanced Institute of Sciences and Technology (KAIST)
contact email	ysyoosik@kaist.ac.kr
lab head
Pavel Sinitcyn
contact affiliation	University of Wisconsin-Madison
contact email	sinitcyn@biochem.mpg.de
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/2023/04/PXD022240

PRIDE project URI

• PRIDE
  1. PXD022240
     1. Label: PRIDE project
     2. Name: Widespread multi-targeted therapy resistance via drug-induced secretome fucosylation