Johnsen, Steven Arthur

[["dc.bibliographiccitation.firstpage","131"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Cell Reports"],["dc.bibliographiccitation.lastpage","139"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Schmidt, Johanna M."],["dc.contributor.author","Panzilius, Elena"],["dc.contributor.author","Bartsch, Harald S."],["dc.contributor.author","Irmler, Martin"],["dc.contributor.author","Beckers, Johannes"],["dc.contributor.author","Kari, Vijayalakshmi"],["dc.contributor.author","Linnemann, Jelena R."],["dc.contributor.author","Dragoi, Diana"],["dc.contributor.author","Hirschi, Benjamin"],["dc.contributor.author","Kloos, Uwe J."],["dc.contributor.author","Sass, Steffen"],["dc.contributor.author","Theis, Fabian J."],["dc.contributor.author","Kahlert, Steffen"],["dc.contributor.author","Johnsen, Steven A."],["dc.contributor.author","Sotlar, Karl"],["dc.contributor.author","Scheel, Christina H."],["dc.date.accessioned","2018-11-07T10:02:12Z"],["dc.date.available","2018-11-07T10:02:12Z"],["dc.date.issued","2015"],["dc.description.abstract","Master regulators of the epithelial-mesenchymal transition such as Twist1 and Snail1 have been implicated in invasiveness and the generation of cancer stem cells, but their persistent activity inhibits stem-cell-like properties and the outgrowth of disseminated cancer cells into macroscopic metastases. Here, we show that Twist1 activation primes a subset of mammary epithelial cells for stem-cell-like properties, which only emerge and stably persist following Twist1 deactivation. Consequently, when cells undergo a mesenchymal-epithelial transition (MET), they do not return to their original epithelial cell state, evidenced by acquisition of invasive growth behavior and a distinct gene expression profile. These data provide an explanation for how transient Twist1 activation may promote all steps of the metastatic cascade; i.e., invasion, dissemination, and metastatic outgrowth at distant sites."],["dc.description.sponsorship","German Cancer Aid Foundation [110225, 111600]"],["dc.identifier.doi","10.1016/j.celrep.2014.12.032"],["dc.identifier.isi","000348036600002"],["dc.identifier.pmid","25578726"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/38183"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Cell Press"],["dc.relation.issn","2211-1247"],["dc.title","Stem-Cell-like Properties and Epithelial Plasticity Arise as Stable Traits after Transient Twist1 Activation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2016"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","2029"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Bedi, Upasana"],["dc.contributor.author","Mishra, Vivek Kumar"],["dc.contributor.author","Wasilewski, David"],["dc.contributor.author","Johnsen, Steven A."],["dc.contributor.author","Scheel, Christina H."],["dc.date.accessioned","2021-11-22T14:31:31Z"],["dc.date.available","2021-11-22T14:31:31Z"],["dc.date.issued","2014-04-30"],["dc.description.abstract","Tumor metastasis is the major cause of mortality and morbidity in most solid cancers. A growing body of evidence suggests that the epithelial-to-mesenchymal transition (EMT) plays a central role during tumor metastasis and frequently imparts a stem cell-like phenotype and therapeutic resistance to tumor cells. The induction of EMT is accompanied by a dynamic reprogramming of the epigenome involving changes in DNA methylation and several post-translational histone modifications. These changes in turn promote the expression of mesenchymal genes or repress those associated with an epithelial phenotype. Importantly, in order for metastatic colonization and the formation of macrometastases to occur, tumor cells frequently undergo a reversal of EMT referred to as the mesenchymal-to-epithelial transition (MET). Thus, a high degree of epigenetic plasticity is required in order to induce and reverse EMT during tumor progression. In this review, we describe various epigenetic regulatory mechanisms employed by tumor cells during EMT and elaborate on the importance of the histone code in controlling both the expression and activity of EMT-associated transcription factors. We propose that a more thorough understanding of the epigenetic mechanisms controlling EMT may provide new opportunities which may be harnessed for improved and individualized cancer therapy based on defined molecular mechanisms."],["dc.identifier.doi","10.18632/oncotarget.1875"],["dc.identifier.fs","610581"],["dc.identifier.isi","000336965800002"],["dc.identifier.pmid","24840099"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12959"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/93384"],["dc.language","eng"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Impact Journals Llc"],["dc.relation.issn","1949-2553"],["dc.rights.access","openAccess"],["dc.subject","Epigenetics; Chromatin; Cancer; Epithelial-to-mesenchymal transition; Metastasis"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Epigenesis, Genetic"],["dc.subject.mesh","Epithelial-Mesenchymal Transition"],["dc.subject.mesh","Gene Expression Regulation, Neoplastic"],["dc.subject.mesh","Humans"],["dc.subject.mesh","Neoplasms"],["dc.title","Epigenetic plasticity: A central regulator of epithelial-to-mesenchymal transition in cancer"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","30396"],["dc.bibliographiccitation.issue","21"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","30407"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Dragoi, Diana"],["dc.contributor.author","Krattenmacher, Anja"],["dc.contributor.author","Mishra, Vivek Kumar"],["dc.contributor.author","Schmidt, Johanna M."],["dc.contributor.author","Kloos, Uwe J."],["dc.contributor.author","Meixner, Lisa K."],["dc.contributor.author","Hauck, Stefanie M."],["dc.contributor.author","Buggenthin, Felix"],["dc.contributor.author","Schwartz, Dennis"],["dc.contributor.author","Marr, Carsten"],["dc.contributor.author","Johnsen, Steven A."],["dc.contributor.author","Scheel, Christina H."],["dc.date.accessioned","2018-11-07T10:14:07Z"],["dc.date.available","2018-11-07T10:14:07Z"],["dc.date.issued","2016"],["dc.description.abstract","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 TGF beta-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 TGF beta-inhibitors as a therapeutic strategy to target invasiveness."],["dc.description.sponsorship","German Cancer Aid Foundation [110225, 111600]"],["dc.identifier.doi","10.18632/oncotarget.8878"],["dc.identifier.isi","000377746600042"],["dc.identifier.pmid","27105506"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14131"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40565"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Impact Journals Llc"],["dc.relation.issn","1949-2553"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Twist1 induces distinct cell states depending on TGFBR1-activation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3130"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Nucleic Acids Research"],["dc.bibliographiccitation.lastpage","3145"],["dc.bibliographiccitation.volume","45"],["dc.contributor.author","Nagarajan, Sankari"],["dc.contributor.author","Bedi, Upasana"],["dc.contributor.author","Budida, Anusha"],["dc.contributor.author","Hamdan, Feda H."],["dc.contributor.author","Mishra, Vivek Kumar"],["dc.contributor.author","Najafova, Zeynab"],["dc.contributor.author","Xie, Wanhua"],["dc.contributor.author","Alawi, Malik"],["dc.contributor.author","Indenbirken, Daniela"],["dc.contributor.author","Knapp, Stefan"],["dc.contributor.author","Chiang, Cheng-Ming"],["dc.contributor.author","Grundhoff, Adam"],["dc.contributor.author","Kari, Vijayalakshmi"],["dc.contributor.author","Scheel, Christina H."],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2018-11-07T10:25:04Z"],["dc.date.available","2018-11-07T10:25:04Z"],["dc.date.issued","2017"],["dc.description.abstract","Bromodomain-containing protein 4 (BRD4) is a member of the bromo-and extraterminal (BET) domain-containing family of epigenetic readers which is under intensive investigation as a target for anti-tumor therapy. BRD4 plays a central role in promoting the expression of select subsets of genes including many driven by oncogenic transcription factors and signaling pathways. However, the role of BRD4 and the effects of BET inhibitors in non-transformed cells remain mostly unclear. We demonstrate that BRD4 is required for the maintenance of a basal epithelial phenotype by regulating the expression of epithelial-specific genes including TP63 and Grainy Head-like transcription factor-3 (GRHL3) in non-transformed basal-like mammary epithelial cells. Moreover, BRD4 occupancy correlates with enhancer activity and enhancer RNA (eRNA) transcription. Motif analyses of cell context-specific BRD4-enriched regions predicted the involvement of FOXOtranscription factors. Consistently, activation of FOXO1 function via inhibition of EGFR-AKT signaling promoted the expression of TP63 and GRHL3. Moreover, activation of Src kinase signaling and FOXO1 inhibition decreased the expression of FOXO/BRD4 target genes. Together, our findings support a function for BRD4 in promoting basal mammary cell epithelial differentiation, at least in part, by regulating FOXO factor function on enhancers to activate TP63 and GRHL3 expression."],["dc.identifier.doi","10.1093/nar/gkw1276"],["dc.identifier.isi","000398376200026"],["dc.identifier.pmid","27980063"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14764"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42778"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Oxford Univ Press"],["dc.relation.issn","1362-4962"],["dc.relation.issn","0305-1048"],["dc.rights","CC BY-NC 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc/4.0"],["dc.title","BRD4 promotes p63 and GRHL3 expression downstream of FOXO in mammary epithelial cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]