PXD006002

PXD006002 is an original dataset announced via ProteomeXchange.

Title	Ambra1 spatially regulates Src activity and Src/FAK-mediated cancer cell invasion via trafficking networks
Description	Here, using mouse squamous cell carcinoma cells, we report a completely new function for the autophagy protein Ambra1 as the first described ‘spatial rheostat’ controlling the Src/FAK pathway. Ambra1 regulates the targeting of active phospho-Src away from focal adhesions into autophagic structures that cancer cells use to survive adhesion stress. Ambra1 binds to both FAK and Src in cancer cells. When FAK is present, Ambra1 is recruited to focal adhesions, promoting FAK-regulated cancer cell direction-sensing and invasion. However, when Ambra1 cannot bind to FAK, abnormally high levels of phospho-Src and phospho-FAK accumulate at focal adhesions, positively regulating adhesion and invasive migration. Spatial control of active Src requires the trafficking proteins Dynactin 1 and IFITM3, which we identified as Ambra1 binding partners by interaction proteomics. We conclude that Ambra1 is a core component of an intracellular trafficking network linked to tight spatial control of active Src and FAK levels, and so crucially regulates their cancer-associated biological outputs.
HostingRepository	PRIDE
AnnounceDate	2017-04-04
AnnouncementXML	Submission_2017-04-04_02:27:31.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Adam Byron
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-03-02 01:32:21	ID requested
⏵ 1	2017-04-04 02:27:33	announced

Schoenherr C, Byron A, Sandilands E, Paliashvili K, Baillie GS, Garcia-Munoz A, Valacca C, Cecconi F, Serrels B, Frame MC, Ambra1 spatially regulates Src activity and Src/FAK-mediated cancer cell invasion via trafficking networks. Elife, 6():(2017) [pubmed]

curator keyword: Biomedical

submitter keyword: Ambra1, Src, FAK, invasion, dynactin 1, IFITM3, trafficking

Margaret C Frame
contact affiliation	Cancer Research UK Edinburgh Centre, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom
contact email	m.frame@ed.ac.uk
lab head
Adam Byron
contact affiliation	University of Edinburgh
contact email	adam.byron@igmm.ed.ac.uk
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/2017/04/PXD006002

PRIDE project URI

• PRIDE
  1. PXD006002
     1. Label: PRIDE project
     2. Name: Ambra1 spatially regulates Src activity and Src/FAK-mediated cancer cell invasion via trafficking networks