PXD051771-1

PXD051771 is an original dataset announced via ProteomeXchange.

Title	N-Glycosylation-Defective IL6 Alternatively Activates the SRC-YAP-SOX2 Axis to Drive Metastasis and EGFR TKI Resistance
Description	The IL6-GP130-STAT3 pathway facilitates lung cancer progression and resistance to tyrosine kinase inhibitors. Although glycosylation alters the stability of GP130, its effect on the ligand IL6 remains unclear. We herein found that N-glycosylated IL6, especially at Asn73, primarily stimulates JAK-STAT3 signaling and prolongs STAT3 phosphorylation, whereas N-glycosylation-defective IL6 (deNG-IL6) induces shortened STAT3 activation and alters the downstream signaling preference for the SRC-YAP-SOX2 axis. This signaling shift induced EMT and migration in vitro and metastasis in vivo, which were suppressed by targeted inhibitors and shRNAs against SRC, YAP, and SOX2. Osimertinib-resistant lung cancer cells secreted a large amount of deNG-IL6 through reduced N-glycosyltransferase gene expression, leading to clear SRC-YAP activation. deNG-IL6 contributes to drug resistance, as confirmed by in silico analysis of cellular and clinical transcriptomes and signal expression in patient specimens. Therefore, the N-glycosylation status of IL6 not only affects cell behaviors but also shows promise in monitoring the dynamics of lung cancer evolution.
HostingRepository	PRIDE
AnnounceDate	2025-01-18
AnnouncementXML	Submission_2025-01-17_18:06:53.857.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD051771
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Cheng-I Daniel Yao
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	deamidated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2024-04-26 01:46:47	ID requested
⏵ 1	2025-01-17 18:06:54	announced

10.1038/s41467-024-51831-7;

10.6019/PXD051771;

Hung CH, Wu SY, Yao CD, Yeh HH, Lin CC, Chu CY, Huang TY, Shen MR, Lin CH, Su WC, Defective N-glycosylation of IL6 induces metastasis and tyrosine kinase inhibitor resistance in lung cancer. Nat Commun, 15(1):7885(2024) [pubmed]

submitter keyword: IL6

glycosylation

lung cancer

EMT

metastasis

EGFR-TKI resistance

SRC

YAP

Chun-Hung Lin
contact affiliation	Institute of Biological Chemistry, Academia Sinica
contact email	chunhung@gate.sinica.edu.tw
lab head
Cheng-I Daniel Yao
contact affiliation	Academia Sinica
contact email	dy0427asu@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD051771
     1. Label: PRIDE project
     2. Name: N-Glycosylation-Defective IL6 Alternatively Activates the SRC-YAP-SOX2 Axis to Drive Metastasis and EGFR TKI Resistance