PXD010401

PXD010401 is an original dataset announced via ProteomeXchange.

Title	Notch2 controls non-autonomous Wnt-signalling in chronic lymphocytic leukaemia
Description	The Wnt-signalling pathway is one of the core de-regulated pathways in chronic lymphocytic leukemia (CLL), activated in a subset of patients by somatic coding mutations. Here we describe an alternative mechanism of Wnt-activation in malignant B cells, mediated by Notch2 activity in mesenchymal stromal cells (MSC) in the tumor microenvironment. We identified that tumor cells specifically induce and activate Notch2 in MSCs. Notch2 orchestrates the expression of target genes essential for the activation of canonical Wnt-signaling in CLL cells. Mechanistically, stromal Notch2 mediates the stabilization of â-catenin by inhibiting the activation of Gsk3-â in malignant B cells. Pharmacological inhibition of the Wnt-pathway mitigates microenvironment-mediated survival of malignant B cells in vitro. Similarly, inhibition of Notch-signaling impaired survival of CLL cells and disease engraftment in a PDX mouse model. Notch2 activation in the tumour microenvironment is a pre-requisite for the GSK3-â dependent activation of the canonical Wnt-signaling in tumor cells.
HostingRepository	PRIDE
AnnounceDate	2018-12-04
AnnouncementXML	Submission_2019-06-03_06:21:53.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD010401
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	James Williamson
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2018-07-12 06:17:33	ID requested
1	2018-12-04 03:46:16	announced
2	2018-12-04 03:51:57	announced	Updated project metadata.
⏵ 3	2019-06-03 06:21:54	announced	Updated project metadata.

Mangolini M, G, ö, tte F, Moore A, Ammon T, Oelsner M, Lutzny-Geier G, Klein-Hitpass L, Williamson JC, Lehner PJ, D, ü, rig J, M, ö, llmann M, R, á, s, ó, -Barnett L, Hughes K, Santoro A, M, é, ndez-Ferrer S, Oostendorp RAJ, Zimber-Strobl U, Peschel C, Hodson DJ, Schmidt-Supprian M, Ringshausen I, Notch2 controls non-autonomous Wnt-signalling in chronic lymphocytic leukaemia. Nat Commun, 9(1):3839(2018) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: NOTCH, WNT, CLL, plasma membrane

Ingo Ringshausen
contact affiliation	Wellcome Trust/ MRC Cambridge Stem Cell Institute & Department of Haematology, Univeristy of Cambridge, Cambridge, UK.
contact email	ir279@cam.ac.uk
lab head
James Williamson
contact affiliation	University of Cambridge
contact email	jcw76@cam.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/2018/09/PXD010401

PRIDE project URI

• PRIDE
  1. PXD010401
     1. Label: PRIDE project
     2. Name: Notch2 controls non-autonomous Wnt-signalling in chronic lymphocytic leukaemia