PXD038687

PXD038687 is an original dataset announced via ProteomeXchange.

Title	The scaffold protein CNK2 promotes cancer cell motility by mediating ARF6 activation downstream of AXL signalling
Description	Cell motility is a critical feature of invasive tumour cells that is governed by complex signal transduction events. Particularly, the underlying mechanisms that bridge extracellular stimuli to the molecular machinery driving motility remain partially understood. Here, we show that the scaffold protein CNK2 promotes cancer cell migration by coupling the pro-metastatic receptor tyrosine kinase AXL to downstream activation of ARF6 GTPase. Mechanistically, AXL signalling induces PI3K-dependent recruitment of CNK2 to the plasma membrane. In turn, CNK2 stimulates ARF6 by associating with cytohesin ARF GEFs and with a novel adaptor protein called SAMD12. ARF6-GTP then controls motile forces by coordinating the respective activation and inhibition of RAC1 and RHOA GTPases. Significantly, genetic ablation of CNK2 or SAMD12 potently reduces metastasis in a mouse xenograft model. Together, this work identifies CNK2 and its partner SAMD12 as key components of a novel pro-motility pathway in cancer cells, which could be targeted in metastasis.
HostingRepository	PRIDE
AnnounceDate	2023-04-20
AnnouncementXML	Submission_2023-04-20_10:27:02.996.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD038687
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	EricBonneil
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; deamidated residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2022-12-08 16:09:07	ID requested
⏵ 1	2023-04-20 10:27:03	announced

10.6019/PXD038687;

submitter keyword: cancer cell motility, AXL signaling,CNK2

MarcTherrien
contact affiliation	IRIC-Université de Montréal
contact email	marc.therrien@umontreal.ca
lab head
EricBonneil
contact affiliation	Proteomic Platform
contact email	eric.bonneil@umontreal.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD038687
     1. Label: PRIDE project
     2. Name: The scaffold protein CNK2 promotes cancer cell motility by mediating ARF6 activation downstream of AXL signalling