PXD018582-1

PXD018582 is an original dataset announced via ProteomeXchange.

Dataset Summary

Title	AXL CONFERS CELL MIGRATION AND INVASION BY HIJACKING A PEAK1-REGULATED FOCAL ADHESION PROTEIN NETWORK
Description	Aberrant expression of receptor tyrosine kinase AXL is linked to metastasis. AXL can be activated by its ligand GAS6 or by other kinases, but the signaling pathways conferring its metastatic activity are unknown. Here, we define the AXL-regulated phosphoproteome in breast cancer cells. We reveal that AXL stimulates the phosphorylation of a network of focal adhesion (FA) proteins culminating in faster FA disassembly. Mechanistically, AXL phosphorylate NEDD9 leading to its binding to CRKII which in turn associates with and orchestrates the phosphorylation of the pseudo-kinase PEAK1. We find that PEAK1 is in complex with the tyrosine kinase CSK to mediate the phosphorylation of PAXILLIN. Uncoupling of PEAK1 from AXL signaling decreases metastasis in vivo, but not tumor growth. Our results uncover a contribution of AXL signaling to FA dynamics, reveal a long sought-after mechanism underlying AXL metastatic activity, and identify PEAK1 as a therapeutic target in AXL positive tumors.
HostingRepository	MassIVE
AnnounceDate	2020-04-15
AnnouncementXML	Submission_2020-04-15_21:05:06.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Jonathan Boulais
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606;
ModificationList	Oxidation; Deamidated; Phospho
Instrument	LTQ Orbitrap Velos; Orbitrap Fusion

Dataset History

Revision	Datetime	Status	ChangeLog Entry
0	2020-04-15 13:04:48	ID requested
⏵ 1	2020-04-15 21:05:07	announced

Publication List

no publication

no publication

Keyword List

submitter keyword: BioID, Phosphoproteomics, PEAK1, NEDD9, AXL, Breast cancer, Focal adhesion, Metastasis

submitter keyword: BioID, Phosphoproteomics, PEAK1, NEDD9, AXL, Breast cancer, Focal adhesion, Metastasis

Contact List

Jean Francois Cote
contact affiliation	IRCM
contact email	Jean-Francois.Cote@ircm.qc.ca
lab head
Jonathan Boulais
contact affiliation	IRCM
contact email	jonathan.boulais@ircm.qc.ca
dataset submitter

Full Dataset Link List

MassIVE dataset URI
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MassIVE dataset URI

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://massive.ucsd.edu/MSV000085293/