PuSH - Publikationsserver des Helmholtz Zentrums München

Export: TXT Text RIS Endnote (RIS) BIB BibTeX
Mangolini, M.* ; Götte, F.* ; Moore, A.* ; Ammon, T.* ; Oelsner, M.* ; Lutzny-Geier, G.* ; Klein-Hitpass, L.* ; Williamson, J.C.* ; Lehner, P.J.* ; Dürig, J.* ; Möllmann, M.* ; Rásó-Barnett, L.* ; Hughes, K.* ; Santoro, A.* ; Méndez-Ferrer, S.* ; Oostendorp, R.A.J.* ; Zimber-Strobl, U. ; Peschel, C.* ; Hodson, D.J.* ; Schmidt-Supprian, M.* ; Ringshausen, I.*

Notch2 controls non-autonomous Wnt-signalling in chronic lymphocytic leukaemia.

Nat. Commun. 9:3839 (2018)
Verlagsversion Forschungsdaten DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
The Wnt signalling pathway, one of the core de-regulated pathways in chronic lymphocytic leukaemia (CLL), is activated in only a subset of patients through somatic mutations. Here we describe alternative, microenvironment-dependent mechanisms of Wnt activation in malignant B cells. We show that tumour cells specifically induce Notch2 activity in mesenchymal stromal cells (MSCs) required for the transcription of the complement factor C1q. MSC-derived C1q in turn inhibits Gsk3-β mediated degradation of β-catenin in CLL cells. Additionally, stromal Notch2 activity regulates N-cadherin expression in CLL cells, which interacts with and further stabilises β-catenin. Together, these stroma Notch2-dependent mechanisms induce strong activation of canonical Wnt signalling in CLL cells. Pharmacological inhibition of the Wnt pathway impairs microenvironment-mediated survival of tumour cells. Similarly, inhibition of Notch signalling diminishes survival of stroma-protected CLL cells in vitro and disease engraftment in vivo. Notch2 activation in the microenvironment is a pre-requisite for the activation of canonical Wnt signalling in tumour cells.
Impact Factor
Scopus SNIP
Scopus
Cited By
Altmetric
12.353
2.912
17
Tags
Anmerkungen
Besondere Publikation
Auf Hompepage verbergern

Zusatzinfos bearbeiten
Eigene Tags bearbeiten
Privat
Eigene Anmerkung bearbeiten
Privat
Auf Publikationslisten für
Homepage nicht anzeigen
Als besondere Publikation
markieren
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Sprache englisch
Veröffentlichungsjahr 2018
HGF-Berichtsjahr 2018
ISSN (print) / ISBN 2041-1723
e-ISSN 2041-1723
Zeitschrift Nature Communications
Quellenangaben Band: 9, Heft: 1, Seiten: , Artikelnummer: 3839 Supplement: ,
Verlag Nature Publishing Group
Verlagsort London
Begutachtungsstatus Peer reviewed
Institut(e) Research Unit Gene Vector (AGV)
POF Topic(s) 30203 - Molecular Targets and Therapies
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-501500-003
DOI 10.1038/s41467-018-06069-5
Scopus ID 85053763141
PubMed ID 30242258
Erfassungsdatum 2018-10-18
[➜Korrektur melden]