PXD079076

PXD079076 is an original dataset announced via ProteomeXchange.

Title	Dissecting early AXL signaling regulators and associated phenotypes in erlotinib-treated EGFR mutant lung cancer by phophosite perturbations
Description	Targeted therapies for receptor tyrosine kinases are effective but invariably limited by drug resistance. In EGFR-mutant lung cancer, AXL activation drives resistance to erlotinib by restoring cell survival and migration. To map these signaling mechanisms, we generated a panel of lung adenocarcinoma PC9 cell lines with phenylalanine substitutions at each intracellular AXL tyrosine residue. By integrating phosphorylation data with phenotypic changes via multivariate modeling, we found that AXL signaling organizes into two clusters enriched for Abl1 and SFK substrate motifs. A peptide specificity screen identified FAK1 as a top proximal substrate of AXL. Downstream, AXL-mediated YAP1 activation was found to sustain drug tolerance, while combined inhibition eliminated persister cells in vitro. These AXL and YAP pathways correlate with disease progression and poor clinical outcomes in erlotinib-treated patients. Collectively, this study dissects the specific signaling regulators by which AXL drives erlotinib resistance.
HostingRepository	PRIDE
AnnounceDate	2026-06-14
AnnouncementXML	Submission_2026-06-14_14:41:01.251.xml
DigitalObjectIdentifier	https://doi.org/10.6019/PXD079076
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Jacqueline Gerritsen
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2026-05-29 22:24:36	ID requested
⏵ 1	2026-06-14 14:41:01	announced

10.6019/PXD079076;

ProteomeXchange project tag: Human Proteome Project

submitter keyword: Computational Modeling, AXL, LUAD, Drug Resistance, Kinase Biology,Systems Biology, EGFR

Forest White
contact affiliation	Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge MA, 02139, USA; Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge MA, 02139, USA; Center for Precision Cancer Medicine, Massachusetts Institute of Technology, Cambridge MA, 02139, USA
contact email	fwhite@mit.edu
lab head
Jacqueline Gerritsen
contact affiliation	Koch Institute, Massachusetts Institute of Technology
contact email	jacqueline.s.gerritsen@gmail.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/2026/06/PXD079076

PRIDE project URI

• PRIDE
  1. PXD079076
     1. Label: PRIDE project
     2. Name: Dissecting early AXL signaling regulators and associated phenotypes in erlotinib-treated EGFR mutant lung cancer by phophosite perturbations