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Dragoi, D. ; Krattenmacher, A. ; Mishra, V.K.* ; Schmidt, J. ; Kloos, U. ; Meixner, L.K. ; Hauck, S.M. ; Buggenthin, F. ; Schwartz, D. ; Marr, C. ; Johnsen, S.A.* ; Scheel, C.

Twist1 induces distinct cell states depending on TGFBR1-activation.

Oncotarget 7, 30396-30407 (2016)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Basic helix-loop-helix transcription factor Twist1 is a master regulator of Epithelial-Mesenchymal Transition (EMT), a cellular program implicated in different stages of development as well as metastatic dissemination of carcinomas. Here, we show that Twist1 requires TGF-beta type-I receptor (TGFBR1)-activation to bind an enhancer region of downstream effector ZEB1, thereby inducing ZEB1 transcription and EMT. When TGFBR1-phosphorylation is inhibited, Twist1 generates a distinct cell state characterized by collective invasion, simultaneous proliferation and expression of endothelial markers. By contrast, TGFBR1-activation directs Twist1 to induce stable mesenchymal transdifferentiation through EMT, thereby generating cells that display single-cell invasion, but lose their proliferative capacity. In conclusion, preventing Twist1-induced EMT by inhibiting TGFβ-signaling does not generally block acquisition of invasion, but switches mode from single-cell/non-proliferative to collective/proliferative. Together, these data reveal that transient Twist1-activation induces distinct cell states depending on signaling context and caution against the use of TGFβ-inhibitors as a therapeutic strategy to target invasiveness.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Tgfbr1 ; Twist1 ; Breast Cancer ; Context Dependence ; Epithelial-mesenchymal Transition; Epithelial-mesenchymal Transition; Growth-factor-beta; Human Breast-cancer; Transcription Factors; Tumor Initiation; E-cadherin; Tgf-beta; Metastasis; Family; Expression
Sprache englisch
Veröffentlichungsjahr 2016
HGF-Berichtsjahr 2016
ISSN (print) / ISBN 1949-2553
e-ISSN 1949-2553
Zeitschrift OncoTarget
Quellenangaben Band: 7, Heft: 21, Seiten: 30396-30407 Artikelnummer: , Supplement: ,
Verlag Impact Journals LLC
Verlagsort Albany
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Stem Cell Research (ISF)
Institute of Computational Biology (ICB)
CF Metabolomics & Proteomics (CF-MPC)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30205 - Bioengineering and Digital Health
30203 - Molecular Targets and Therapies
Forschungsfeld(er) Stem Cell and Neuroscience
Enabling and Novel Technologies
PSP-Element(e) G-552300-001
G-503800-001
G-505700-001
PubMed ID 27105506
DOI 10.18632/oncotarget.8878
WOS ID WOS:000377746600042
Scopus ID 84971500246
Erfassungsdatum 2016-05-10
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