Heßmann, Elisabeth

[["dc.bibliographiccitation.firstpage","1470"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Leukemia"],["dc.bibliographiccitation.lastpage","1477"],["dc.bibliographiccitation.volume","29"],["dc.contributor.author","Metzelder, S. K."],["dc.contributor.author","Michel, C."],["dc.contributor.author","von Bonin, Malte"],["dc.contributor.author","Rehberger, M."],["dc.contributor.author","Hessmann, Elisabeth"],["dc.contributor.author","Inselmann, S."],["dc.contributor.author","Solovey, M."],["dc.contributor.author","Wang, Y."],["dc.contributor.author","Sohlbach, K."],["dc.contributor.author","Brendel, Cornelia"],["dc.contributor.author","Stiewe, Thorsten"],["dc.contributor.author","Charles, J."],["dc.contributor.author","Ten Haaf, A."],["dc.contributor.author","Ellenrieder, Volker"],["dc.contributor.author","Neubauer, A."],["dc.contributor.author","Gattenloehner, Stefan"],["dc.contributor.author","Bornhaeuser, Martin"],["dc.contributor.author","Burchert, Andreas"],["dc.date.accessioned","2018-11-07T09:55:10Z"],["dc.date.available","2018-11-07T09:55:10Z"],["dc.date.issued","2015"],["dc.description.abstract","Internal tandem duplications (ITD) in the Fms-related tyrosine kinase 3 receptor (FLT3) are associated with a dismal prognosis in acute myeloid leukemia (AML). FLT3 inhibitors such as sorafenib may improve outcome, but only few patients display long-term responses, prompting the search for underlying resistance mechanisms and therapeutic strategies to overcome them. Here we identified that the nuclear factor of activated T cells, NFATc1, is frequently overexpressed in FLT3-ITD-positive (FLT3-ITD+) AML. NFATc1 knockdown using inducible short hairpin RNA or pharmacological NFAT inhibition with cyclosporine A (CsA) or VIVIT significantly augmented sorafenib-induced apoptosis of FLT3-ITD+ cells. CsA also potently overcame sorafenib resistance in FLT3-ITD+ cell lines and primary AML. Vice versa, de novo expression of a constitutively nuclear NFATc1-mutant mediated instant and robust sorafenib resistance in vitro. Intriguingly, FLT3-ITD+ AML patients (n = 26) who received CsA as part of their rescue chemotherapy displayed a superior outcome when compared with wild-type FLT3 (FLT3-WT) AML patients. Our data unveil NFATc1 as a novel mediator of sorafenib resistance in FLT3-ITD+ AML. CsA counteracts sorafenib resistance and may improve treatment outcome in AML by means of inhibiting NFAT."],["dc.identifier.doi","10.1038/leu.2015.95"],["dc.identifier.isi","000357623100006"],["dc.identifier.pmid","25976987"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36691"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1476-5551"],["dc.relation.issn","0887-6924"],["dc.title","NFATc1 as a therapeutic target in FLT3-ITD-positive AML"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","eLife"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Zhang, Zhe"],["dc.contributor.author","Hessmann, Elisabeth"],["dc.date.accessioned","2020-12-10T18:48:06Z"],["dc.date.available","2020-12-10T18:48:06Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.7554/eLife.38967"],["dc.identifier.eissn","2050-084X"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/79019"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","To be or not to be"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","484"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","EBioMedicine"],["dc.bibliographiccitation.lastpage","485"],["dc.bibliographiccitation.volume","2"],["dc.contributor.author","Neesse, A."],["dc.contributor.author","Hessmann, E."],["dc.date.accessioned","2021-04-26T11:54:21Z"],["dc.date.available","2021-04-26T11:54:21Z"],["dc.date.issued","2015-06"],["dc.identifier.doi","10.1016/j.ebiom.2015.05.017"],["dc.identifier.pmid","26288808"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/84361"],["dc.language.iso","en"],["dc.relation.issn","2352-3964"],["dc.title","Electron Transfer-Based Compounds: A Novel Weapon in the Cancer Battlespace?"],["dc.type","journal_article"],["dc.type.internalPublication","no"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","canres.2874.2020"],["dc.bibliographiccitation.journal","Cancer Research"],["dc.contributor.author","Kutschat, Ana P."],["dc.contributor.author","Hamdan, Feda H."],["dc.contributor.author","Wang, Xin"],["dc.contributor.author","Wixom, Alexander Q."],["dc.contributor.author","Najafova, Zeynab"],["dc.contributor.author","Gibhardt, Christine S."],["dc.contributor.author","Kopp, Waltraut"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Ströbel, Philipp"],["dc.contributor.author","Ellenrieder, Volker"],["dc.contributor.author","Bogeski, Ivan"],["dc.contributor.author","Hessmann, Elisabeth"],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2021-04-26T11:54:17Z"],["dc.date.available","2021-04-26T11:54:17Z"],["dc.date.issued","2021-01-12"],["dc.description.abstract","Pancreatic Ductal Adenocarcinoma (PDAC) displays a dismal prognosis due to late diagnosis and high chemoresistance incidence. For advanced disease stages or patients with comorbidities, treatment options are limited to gemcitabine alone or in combination with other drugs. While gemcitabine resistance has been widely attributed to the levels of one of its targets, RRM1, the molecular consequences of gemcitabine resistance in PDAC remain largely elusive. Here we sought to identify genomic, epigenomic, and transcriptomic events associated with gemcitabine resistance in PDAC and their potential clinical relevance. We found that gemcitabine-resistant cells displayed a co-amplification of the adjacent RRM1 and STIM1 genes. Interestingly, RRM1, but not STIM1, was required for gemcitabine resistance, while high STIM1 levels caused an increase in cytosolic calcium concentration. Higher STIM1-dependent calcium influx led to an impaired ER stress response and a heightened NFAT activity. Importantly, these findings were confirmed in patient and patient-derived xenograft samples. Taken together, our study uncovers previously unknown biologically relevant molecular properties of gemcitabine-resistant tumors, revealing an undescribed function of STIM1 as a rheostat directing the effects of calcium signaling and controlling epigenetic cell fate determination. It further reveals the potential benefit of targeting STIM1-controlled calcium signaling and its downstream effectors in PDAC."],["dc.identifier.doi","10.1158/0008-5472.CAN-20-2874"],["dc.identifier.pmid","33436389"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/84360"],["dc.language.iso","en"],["dc.relation.eissn","1538-7445"],["dc.relation.issn","0008-5472"],["dc.title","STIM1 Mediates Calcium-dependent Epigenetic Reprogramming in Pancreatic Cancer"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["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","1481"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Molecular Cancer Research"],["dc.bibliographiccitation.lastpage","1490"],["dc.bibliographiccitation.volume","15"],["dc.contributor.author","Emons, Georg"],["dc.contributor.author","Spitzner, Melanie"],["dc.contributor.author","Reineke, Sebastian"],["dc.contributor.author","Möller, Janneke"],["dc.contributor.author","Auslander, Noam"],["dc.contributor.author","Kramer, Frank"],["dc.contributor.author","Hu, Yue"],["dc.contributor.author","Beissbarth, Tim"],["dc.contributor.author","Wolff, Hendrik A."],["dc.contributor.author","Rave-Fränk, Margret"],["dc.contributor.author","Heßmann, Elisabeth"],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Ghadimi, B. Michael"],["dc.contributor.author","Johnsen, Steven A."],["dc.contributor.author","Ried, Thomas"],["dc.contributor.author","Grade, Marian"],["dc.date.accessioned","2020-12-10T18:37:47Z"],["dc.date.available","2020-12-10T18:37:47Z"],["dc.date.issued","2017"],["dc.description.abstract","Activation of Wnt/β-catenin signaling plays a central role in the development and progression of colorectal cancer. The Wnt-transcription factor, TCF7L2, is overexpressed in primary rectal cancers that are resistant to chemoradiotherapy and TCF7L2 mediates resistance to chemoradiotherapy. However, it is unclear whether the resistance is mediated by a TCF7L2 inherent mechanism or Wnt/β-catenin signaling in general. Here, inhibition of β-catenin by siRNAs or a small-molecule inhibitor (XAV-939) resulted in sensitization of colorectal cancer cells to chemoradiotherapy. To investigate the potential role of Wnt/β-catenin signaling in controlling therapeutic responsiveness, nontumorigenic RPE-1 cells were stimulated with Wnt-3a, a physiologic ligand of Frizzled receptors, which increased resistance to chemoradiotherapy. This effect could be recapitulated by overexpression of a degradation-resistant mutant of β-catenin (S33Y), also boosting resistance of RPE-1 cells to chemoradiotherapy, which was, conversely, abrogated by siRNA-mediated silencing of β-catenin. Consistent with these findings, higher expression levels of active β-catenin were observed as well as increased TCF/LEF reporter activity in SW1463 cells that evolved radiation resistance due to repeated radiation treatment. Global gene expression profiling identified several altered pathways, including PPAR signaling and other metabolic pathways, associated with cellular response to radiation. In summary, aberrant activation of Wnt/β-catenin signaling not only regulates the development and progression of colorectal cancer, but also mediates resistance of rectal cancers to chemoradiotherapy.Implications: Targeting Wnt/β-catenin signaling or one of the downstream pathways represents a promising strategy to increase response to chemoradiotherapy. Mol Cancer Res; 15(11); 1481-90. ©2017 AACR."],["dc.identifier.doi","10.1158/1541-7786.MCR-17-0205"],["dc.identifier.eissn","1557-3125"],["dc.identifier.issn","1541-7786"],["dc.identifier.pmid","28811361"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77090"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.relation.eissn","1557-3125"],["dc.relation.issn","1541-7786"],["dc.title","Chemoradiotherapy Resistance in Colorectal Cancer Cells is Mediated by Wnt/β-catenin Signaling"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1024"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Gastroenterology"],["dc.bibliographiccitation.lastpage","U502"],["dc.bibliographiccitation.volume","148"],["dc.contributor.author","Chen, Nai-Ming"],["dc.contributor.author","Singh, Garima"],["dc.contributor.author","Koenig, Alexander O."],["dc.contributor.author","Liou, Geou-Yarh"],["dc.contributor.author","Storz, Peter"],["dc.contributor.author","Zhang, J."],["dc.contributor.author","Regul, Lisanne"],["dc.contributor.author","Nagarajan, Sankari"],["dc.contributor.author","Kuehnemuth, Benjamin"],["dc.contributor.author","Johnsen, Steven A."],["dc.contributor.author","Hebrok, Matthias"],["dc.contributor.author","Siveke, Jens T."],["dc.contributor.author","Billadeau, Daniel D."],["dc.contributor.author","Ellenrieder, Volker"],["dc.contributor.author","Heßmann, Elisabeth"],["dc.date.accessioned","2018-11-07T09:57:58Z"],["dc.date.available","2018-11-07T09:57:58Z"],["dc.date.issued","2015"],["dc.description.abstract","BACKGROUND & AIMS: Oncogenic mutations in KRAS contribute to the development of pancreatic ductal adenocarcinoma, but are not sufficient to initiate carcinogenesis. Secondary events, such as inflammation-induced signaling via the epidermal growth factor receptor (EGFR) and expression of the SOX9 gene, are required for tumor formation. Herein we sought to identify the mechanisms that link EGFR signaling with activation of SOX9 during acinar-ductal metaplasia, a transdifferentiation process that precedes pancreatic carcinogenesis. METHODS: We analyzed pancreatic tissues from KrasG12D; pdx1-Cre and KrasG12D; NFATc1D/D; pdx1-Cre mice after intraperitoneal administration of caerulein, vs cyclosporin A or dimethyl sulfoxide (controls). Induction of EGFR signaling and its effects on the expression of Nuclear factor of activated T cells c1 (NFATc1) or SOX9 were investigated by quantitative reverse-transcription polymerase chain reaction, immunoblot, and immunohistochemical analyses of mouse and human tissues and acinar cell explants. Interactions between NFATc1 and partner proteins and effects on DNA binding or chromatin modifications were studied using co-immunoprecipitation and chromatin immunoprecipitation assays in acinar cell explants and mouse tissue. RESULTS: EGFR activation induced expression of NFATc1 in metaplastic areas from patients with chronic pancreatitis and in pancreatic tissue from KrasG12D mice. EGFR signaling also promoted formation of a complex between NFATc1 and C-JUN in dedifferentiating mouse acinar cells, leading to activation of Sox9 transcription and induction of acinar-ductal metaplasia. Pharmacologic inhibition of NFATc1 or disruption of the Nfatc1 gene inhibited EGFR-mediated induction of Sox9 transcription and blocked acinar-ductal transdifferentiation and pancreatic cancer initiation in mice. CONCLUSIONS: EGFR signaling induces expression of NFATc1 and Sox9, leading to acinar cell transdifferentiation and initiation of pancreatic cancer. Strategies designed to disrupt this pathway might be developed to prevent pancreatic cancer initiation in high-risk patients with chronic pancreatitis."],["dc.identifier.doi","10.1053/j.gastro.2015.01.033"],["dc.identifier.isi","000353335700033"],["dc.identifier.pmid","25623042"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37276"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","W B Saunders Co-elsevier Inc"],["dc.relation.issn","1528-0012"],["dc.relation.issn","0016-5085"],["dc.title","NFATc1 Links EGFR Signaling to Induction of Sox9 Transcription and Acinar-Ductal Transdifferentiation in the Pancreas"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1609"],["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","Oncogene"],["dc.bibliographiccitation.lastpage","1618"],["dc.bibliographiccitation.volume","35"],["dc.contributor.author","Hessmann, Elisabeth"],["dc.contributor.author","Schneider, G."],["dc.contributor.author","Ellenrieder, Volker"],["dc.contributor.author","Siveke, Jens T."],["dc.date.accessioned","2018-11-07T10:16:40Z"],["dc.date.available","2018-11-07T10:16:40Z"],["dc.date.issued","2016"],["dc.description.abstract","Owing to its aggressiveness, late detection and marginal therapeutic accessibility, pancreatic ductal adenocarcinoma (PDAC) remains a most challenging malignant disease. Despite scientific progress in the understanding of the mechanisms that underly PDAC initiation and progression, the successful translation of experimental findings into effective new therapeutic strategies remains a largely unmet need. The oncogene MYC is activated in many PDAC cases and is a master regulator of vital cellular processes. Excellent recent studies have shed new light on the tremendous functions of MYC in cancer and identified inhibition of MYC as a likewise beneficial and demanding effort. This review will focus on mechanisms that contribute to deregulation of MYC expression in pancreatic carcinogenesis and progression and will summarize novel biological findings from recent in vivo models. Finally, we provide a perspective, how regulation of MYC in PDAC may contribute to the development of new therapeutic approaches."],["dc.identifier.doi","10.1038/onc.2015.216"],["dc.identifier.isi","000373064200001"],["dc.identifier.pmid","26119937"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41079"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1476-5594"],["dc.relation.issn","0950-9232"],["dc.title","MYC in pancreatic cancer: novel mechanistic insights and their translation into therapeutic strategies"],["dc.type","review"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Neuroendocrinology"],["dc.bibliographiccitation.volume","103"],["dc.contributor.author","Koenig, A."],["dc.contributor.author","Heßmann, Elisabeth"],["dc.contributor.author","Hanheide, S."],["dc.contributor.author","Gaedcke, Jochen"],["dc.contributor.author","Zhang, J."],["dc.contributor.author","Billadeau, Daniel D."],["dc.contributor.author","Ellenrieder, Volker"],["dc.date.accessioned","2018-11-07T10:19:54Z"],["dc.date.available","2018-11-07T10:19:54Z"],["dc.date.issued","2016"],["dc.format.extent","7"],["dc.identifier.isi","000386481600017"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41763"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Karger"],["dc.publisher.place","Basel"],["dc.relation.conference","13th Annual ENETS Conference for the Diagnosis and Treatment of Neuroendocrine Tumor Disease"],["dc.relation.eventlocation","Barcelona, SPAIN"],["dc.relation.issn","1423-0194"],["dc.relation.issn","0028-3835"],["dc.title","mTOR Controls an Epigenetic Program Leading to Autophagy and Cell Growth Control"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Gastroenterology"],["dc.contributor.author","Hessmann, Elisabeth"],["dc.contributor.author","Schneider, Günter"],["dc.date.accessioned","2021-07-05T15:00:37Z"],["dc.date.available","2021-07-05T15:00:37Z"],["dc.date.issued","2021"],["dc.identifier.doi","10.1053/j.gastro.2021.04.082"],["dc.identifier.pii","S0016508521030754"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/87866"],["dc.language.iso","en"],["dc.notes.intern","DOI Import DOI-Import GROB-441"],["dc.relation.issn","0016-5085"],["dc.title","New insights into pancreatic cancer: notes from a virtual meeting."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]