Heßmann, Elisabeth

[["dc.bibliographiccitation.firstpage","688"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Cancer Discovery"],["dc.bibliographiccitation.lastpage","701"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Baumgart, Sandra"],["dc.contributor.author","Chen, Nai-Ming"],["dc.contributor.author","Siveke, Jens T."],["dc.contributor.author","Koenig, Alexander O."],["dc.contributor.author","Zhang, J."],["dc.contributor.author","Singh, Shiv K."],["dc.contributor.author","Wolf, Elmar"],["dc.contributor.author","Bartkuhn, Marek"],["dc.contributor.author","Esposito, Irene"],["dc.contributor.author","Hessmann, Elisabeth"],["dc.contributor.author","Reinecke, Johanna"],["dc.contributor.author","Nikorowitsch, Julius"],["dc.contributor.author","Brunner, Marius"],["dc.contributor.author","Singh, Garima"],["dc.contributor.author","Fernandez-Zapico, Martin E."],["dc.contributor.author","Smyrk, Thomas C."],["dc.contributor.author","Bamlet, William R."],["dc.contributor.author","Eilers, Martin"],["dc.contributor.author","Neesse, Albrecht"],["dc.contributor.author","Gress, Thomas M."],["dc.contributor.author","Billadeau, Daniel D."],["dc.contributor.author","Tuveson, David A."],["dc.contributor.author","Urrutia, Raul"],["dc.contributor.author","Ellenrieder, Volker"],["dc.date.accessioned","2018-11-07T09:39:31Z"],["dc.date.available","2018-11-07T09:39:31Z"],["dc.date.issued","2014"],["dc.description.abstract","Cancer-associated inflammation is a molecular key feature in pancreatic ductal adenocarcinoma. Oncogenic KRAS in conjunction with persistent inflammation is known to accelerate carcinogenesis, although the underlying mechanisms remain poorly understood. Here, we outline a novel pathway whereby the transcription factors NFATc1 and STAT3 cooperate in pancreatic epithelial cells to promote Kras(G12D) -driven carcinogenesis. NFATc1 activation is induced by inflammation and itself accelerates inflammation-induced carcinogenesis in Kras(G12D) mice, whereas genetic or pharmacologic ablation of NFATc1 attenuates this effect. Mechanistically, NFATc1 complexes with STAT3 for enhancer-promoter communications at jointly regulated genes involved in oncogenesis, for example, Cyclin, EGFR and WNT family members. The NFATc1-STAT3 cooperativity is operative in pancreatitis-mediated carcinogenesis as well as in established human pancreatic cancer. Together, these studies unravel new mechanisms of inflammatory-driven pancreatic carcinogenesis and suggest beneficial effects of chemopreventive strategies using drugs that are currently available for targeting these factors in clinical trials. SIGNIFICANCE: Our study points to the existence of an oncogenic NFATc1-STAT3 cooperativity that mechanistically links inflammation with pancreatic cancer initiation and progression. Because NFATc1STAT3 nucleoprotein complexes control the expression of gene networks at the intersection of inflammation and cancer, our study has significant relevance for potentially managing pancreatic cancer and other inflammatory-driven malignancies. (C) 2014 AACR."],["dc.identifier.doi","10.1158/2159-8290.CD-13-0593"],["dc.identifier.isi","000337185500025"],["dc.identifier.pmid","24694735"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/33304"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Cancer Research"],["dc.relation.issn","2159-8290"],["dc.relation.issn","2159-8274"],["dc.title","Inflammation-Induced NFATc1-STAT3 Transcription Complex Promotes Pancreatic Cancer Initiation by Kras(G12D)"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","491"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Molecular Cancer Therapeutics"],["dc.bibliographiccitation.lastpage","502"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","Zhang, L."],["dc.contributor.author","Baumgart, Sandra"],["dc.contributor.author","Chen, Nai-Ming"],["dc.contributor.author","Zhang, J."],["dc.contributor.author","Billadeau, Daniel D."],["dc.contributor.author","Gaisina, Irina N."],["dc.contributor.author","Kozikowski, Alan P."],["dc.contributor.author","Singh, Shiv K."],["dc.contributor.author","Fink, Daniel"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Klindt, Caroline"],["dc.contributor.author","Bamlet, William R."],["dc.contributor.author","König, Alexander O."],["dc.contributor.author","Heßmann, Elisabeth"],["dc.contributor.author","Gress, Thomas M."],["dc.contributor.author","Ellenrieder, Volker"],["dc.contributor.author","Neeße, Albrecht"],["dc.date.accessioned","2020-12-10T18:37:46Z"],["dc.date.available","2020-12-10T18:37:46Z"],["dc.date.issued","2016"],["dc.description.abstract","We aimed to investigate the mechanistic, functional, and therapeutic role of glycogen synthase kinase 3 beta (GSK-3 beta) in the regulation and activation of the proinflammatory oncogenic transcription factor nuclear factor of activated T cells (NFATc2) in pancreatic cancer. IHC, qPCR, immunoblotting, immunofluorescence microscopy, and proliferation assays were used to analyze mouse and human tissues and cell lines. Protein-protein interactions and promoter regulation were analyzed by coimmunoprecipitation, DNA pulldown, reporter, and ChIP assays. Preclinical assays were performed using a variety of pancreatic cancer cells lines, xenografts, and a genetically engineered mouse model (GEMM). GSK-3 beta-dependent SP2 phosphorylationmediates NFATc2 protein stability in the nucleus of pancreatic cancer cells stimulating pancreatic cancer growth. In addition to protein stabilization, GSK-3 beta also maintains NFATc2 activation through a distinct mechanism involving stabilization of NFATc2-STAT3 complexes independent of SP2 phosphorylation. For NFATc2-STAT3 complex formation, GSK-3 beta-mediated phosphorylation of STAT3 at Y705 is required to stimulate euchromatin formation of NFAT target promoters, such as cyclin-dependent kinase-6, which promotes tumor growth. Finally, preclinical experiments suggest that targeting the NFATc2-STAT3-GSK-3b module inhibits proliferation and tumor growth and interferes with inflammation-induced pancreatic cancer progression in Kras(G12D) mice. In conclusion, we describe a novel mechanism by which GSK3 beta fine-tunes NFATc2 and STAT3 transcriptional networks to integrate upstream signaling events that govern pancreatic cancer progression and growth. Furthermore, the therapeutic potential of GSK-3 beta is demonstrated for the first time in a relevant Kras and inflammation-induced GEMM for pancreatic cancer. (C) 2016 AACR."],["dc.identifier.doi","10.1158/1535-7163.MCT-15-0309"],["dc.identifier.eissn","1538-8514"],["dc.identifier.isi","000373595600015"],["dc.identifier.issn","1535-7163"],["dc.identifier.pmid","26823495"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77088"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Cancer Research"],["dc.relation.issn","1538-8514"],["dc.relation.issn","1535-7163"],["dc.title","GSK-3 beta Governs Inflammation-Induced NFATc2 Signaling Hubs to Promote Pancreatic Cancer Progression"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","4620"],["dc.bibliographiccitation.issue","21"],["dc.bibliographiccitation.journal","Cancer Research"],["dc.bibliographiccitation.lastpage","4632"],["dc.bibliographiccitation.volume","80"],["dc.contributor.author","Patil, Shilpa"],["dc.contributor.author","Steuber, Benjamin"],["dc.contributor.author","Kopp, Waltraut"],["dc.contributor.author","Kari, Vijayalakshmi"],["dc.contributor.author","Urbach, Laura"],["dc.contributor.author","Wang, Xin"],["dc.contributor.author","Küffer, Stefan"],["dc.contributor.author","Bohnenberger, Hanibal"],["dc.contributor.author","Spyropoulou, Dimitra"],["dc.contributor.author","Zhang, Zhe"],["dc.contributor.author","Versemann, Lennart"],["dc.contributor.author","Bösherz, Mark Sebastian"],["dc.contributor.author","Brunner, Marius"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Zhang, Jin-San"],["dc.contributor.author","Neesse, Albrecht"],["dc.contributor.author","Ellenrieder, Volker"],["dc.contributor.author","Singh, Shiv K."],["dc.contributor.author","Johnsen, Steven A."],["dc.contributor.author","Hessmann, Elisabeth"],["dc.date.accessioned","2021-04-14T08:31:24Z"],["dc.date.available","2021-04-14T08:31:24Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1158/0008-5472.CAN-20-0672"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/83584"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1538-7445"],["dc.relation.issn","0008-5472"],["dc.title","EZH2 Regulates Pancreatic Cancer Subtype Identity and Tumor Progression via Transcriptional Repression of GATA6"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1707"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Physiological Reviews"],["dc.bibliographiccitation.lastpage","1751"],["dc.bibliographiccitation.volume","100"],["dc.contributor.author","Hessmann, Elisabeth"],["dc.contributor.author","Buchholz, Soeren M."],["dc.contributor.author","Demir, Ihsan Ekin"],["dc.contributor.author","Singh, Shiv K."],["dc.contributor.author","Gress, Thomas M."],["dc.contributor.author","Ellenrieder, Volker"],["dc.contributor.author","Neesse, Albrecht"],["dc.date.accessioned","2021-04-14T08:32:51Z"],["dc.date.available","2021-04-14T08:32:51Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1152/physrev.00042.2019"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/84035"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1522-1210"],["dc.relation.issn","0031-9333"],["dc.title","Microenvironmental Determinants of Pancreatic Cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","517"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","The EMBO Journal"],["dc.bibliographiccitation.lastpage","530"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Singh, Shiv K."],["dc.contributor.author","Chen, Nai-Ming"],["dc.contributor.author","Heßmann, Elisabeth"],["dc.contributor.author","Siveke, Jens T."],["dc.contributor.author","Lahmann, Marlen"],["dc.contributor.author","Singh, Garima"],["dc.contributor.author","Voelker, Nadine"],["dc.contributor.author","Vogt, Sophia"],["dc.contributor.author","Esposito, Irene"],["dc.contributor.author","Schmidt, Ansgar"],["dc.contributor.author","Brendel, Cornelia"],["dc.contributor.author","Stiewe, Thorsten"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Mernberger, Marco"],["dc.contributor.author","Crawford, Howard C."],["dc.contributor.author","Bamlet, William R."],["dc.contributor.author","Zhang, J."],["dc.contributor.author","Li, Xiao-Kun"],["dc.contributor.author","Smyrk, Thomas C."],["dc.contributor.author","Billadeau, Daniel D."],["dc.contributor.author","Hebrok, Matthias"],["dc.contributor.author","Neeße, Albrecht"],["dc.contributor.author","Koenig, Alexander O."],["dc.contributor.author","Ellenrieder, Volker"],["dc.date.accessioned","2018-11-07T10:00:56Z"],["dc.date.available","2018-11-07T10:00:56Z"],["dc.date.issued","2015"],["dc.description.abstract","In adaptation to oncogenic signals, pancreatic ductal adenocarcinoma (PDAC) cells undergo epithelial-mesenchymal transition (EMT), a process combining tumor cell dedifferentiation with acquisition of stemness features. However, the mechanisms linking oncogene-induced signaling pathways with EMT and stemness remain largely elusive. Here, we uncover the inflammation-induced transcription factor NFATc1 as a central regulator of pancreatic cancer cell plasticity. In particular, we show that NFATc1 drives EMT reprogramming and maintains pancreatic cancer cells in a stem cell-like state through Sox2-dependent transcription of EMT and stemness factors. Intriguingly, NFATc1-Sox2 complex-mediated PDAC dedifferentiation and progression is opposed by antithetical p53-miR200c signaling, and inactivation of the tumor suppressor pathway is essential for tumor dedifferentiation and dissemination both in genetically engineered mouse models (GEMM) and human PDAC. Based on these findings, we propose the existence of a hierarchical signaling network regulating PDAC cell plasticity and suggest that the molecular decision between epithelial cell preservation and conversion into a dedifferentiated cancer stem cell-like phenotype depends on opposing levels of p53 and NFATc1 signaling activities."],["dc.identifier.doi","10.15252/embj.201489574"],["dc.identifier.isi","000349695100009"],["dc.identifier.pmid","25586376"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37913"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley"],["dc.relation.issn","1460-2075"],["dc.relation.issn","0261-4189"],["dc.title","Antithetical NFATc1-Sox2 and p53-miR200 signaling networks govern pancreatic cancer cell plasticity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]