Kube, Dieter

[["dc.bibliographiccitation.artnumber","1514"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature communications"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Feist, Maren"],["dc.contributor.author","Schwarzfischer, Philipp"],["dc.contributor.author","Heinrich, Paul"],["dc.contributor.author","Sun, Xueni"],["dc.contributor.author","Kemper, Judith"],["dc.contributor.author","von Bonin, Frederike"],["dc.contributor.author","Perez-Rubio, Paula"],["dc.contributor.author","Taruttis, Franziska"],["dc.contributor.author","Rehberg, Thorsten"],["dc.contributor.author","Dettmer, Katja"],["dc.contributor.author","Gronwald, Wolfram"],["dc.contributor.author","Reinders, Jörg"],["dc.contributor.author","Engelmann, Julia C."],["dc.contributor.author","Dudek, Jan"],["dc.contributor.author","Klapper, Wolfram"],["dc.contributor.author","Trümper, Lorenz"],["dc.contributor.author","Spang, Rainer"],["dc.contributor.author","Oefner, Peter J."],["dc.contributor.author","Kube, Dieter"],["dc.date.accessioned","2019-07-09T11:45:23Z"],["dc.date.available","2019-07-09T11:45:23Z"],["dc.date.issued","2018"],["dc.description.abstract","Knowledge of stromal factors that have a role in the transcriptional regulation of metabolic pathways aside from c-Myc is fundamental to improvements in lymphoma therapy. Using a MYC-inducible human B-cell line, we observed the cooperative activation of STAT3 and NF-κB by IL10 and CpG stimulation. We show that IL10 + CpG-mediated cell proliferation of MYClow cells depends on glutaminolysis. By 13C- and 15N-tracing of glutamine metabolism and metabolite rescue experiments, we demonstrate that GOT2 provides aspartate and nucleotides to cells with activated or aberrant Jak/STAT and NF-κB signaling. A model of GOT2 transcriptional regulation is proposed, in which the cooperative phosphorylation of STAT3 and direct joint binding of STAT3 and p65/NF-κB to the proximal GOT2 promoter are important. Furthermore, high aberrant GOT2 expression is prognostic in diffuse large B-cell lymphoma underscoring the current findings and importance of stromal factors in lymphoma biology."],["dc.identifier.doi","10.1038/s41467-018-03803-x"],["dc.identifier.pmid","29666362"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15191"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59220"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2041-1723"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.title","Cooperative STAT/NF-κB signaling regulates lymphoma metabolic reprogramming and aberrant GOT2 expression."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1480"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","EMBO Molecular Medicine"],["dc.bibliographiccitation.lastpage","1502"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Isernhagen, Antje"],["dc.contributor.author","Malzahn, Doerthe"],["dc.contributor.author","Viktorova, Elena"],["dc.contributor.author","Elsner, Leslie"],["dc.contributor.author","Monecke, Sebastian"],["dc.contributor.author","von Bonin, Frederike"],["dc.contributor.author","Kilisch, Markus"],["dc.contributor.author","Wermuth, Janne Marieke"],["dc.contributor.author","Walther, Neele"],["dc.contributor.author","Balavarca, Yesilda"],["dc.contributor.author","Stahl-Hennig, Christiane"],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Walter, Lutz"],["dc.contributor.author","Bickeboeller, Heike"],["dc.contributor.author","Kube, Dieter"],["dc.contributor.author","Wulf, Gerald"],["dc.contributor.author","Dressel, Ralf"],["dc.date.accessioned","2018-11-07T09:49:36Z"],["dc.date.available","2018-11-07T09:49:36Z"],["dc.date.issued","2015"],["dc.description.abstract","The MHC class I chain-related molecule A (MICA) is a highly polymorphic ligand for the activating natural killer (NK)-cell receptor NKG2D. A single nucleotide polymorphism causes a valine to methionine exchange at position 129. Presence of a MICA-129Met allele in patients (n=452) undergoing hematopoietic stem cell transplantation (HSCT) increased the chance of overall survival (hazard ratio [HR]=0.77, P=0.0445) and reduced the risk to die due to acute graft-versus-host disease (aGVHD) (odds ratio [OR]=0.57, P=0.0400) although homozygous carriers had an increased risk to experience this complication (OR=1.92, P=0.0371). Overall survival of MICA-129Val/Val genotype carriers was improved when treated with anti-thymocyte globulin (HR=0.54, P=0.0166). Functionally, the MICA-129Met isoform was characterized by stronger NKG2D signaling, triggering more NK-cell cytotoxicity and interferon- release, and faster co-stimulation of CD8(+) T cells. The MICA-129Met variant also induced a faster and stronger down-regulation of NKG2D on NK and CD8(+) T cells than the MICA-129Val isoform. The reduced cell surface expression of NKG2D in response to engagement by MICA-129Met variants appeared to reduce the severity of aGVHD."],["dc.description.sponsorship","Open-Access Publikationsfonds 2015"],["dc.identifier.doi","10.15252/emmm.201505246"],["dc.identifier.isi","000364320100008"],["dc.identifier.pmid","26483398"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12462"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35542"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/127"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | C05: Bedeutung von zellulären Immunreaktionen für das kardiale Remodeling und die Therapie der Herzinsuffizienz durch Stammzelltransplantation"],["dc.relation.issn","1757-4684"],["dc.relation.issn","1757-4676"],["dc.relation.workinggroup","RG Dressel"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","The MICA-129 dimorphism affects NKG2D signaling and outcome of hematopoietic stem cell transplantation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Oncology Research and Treatment"],["dc.bibliographiccitation.volume","38"],["dc.contributor.author","Linke, F."],["dc.contributor.author","Zaunig, S."],["dc.contributor.author","von Bonin, Frederike"],["dc.contributor.author","Wilting, J."],["dc.contributor.author","Bryja, V."],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Truemper, Lorenz H."],["dc.contributor.author","Kube, Dieter"],["dc.date.accessioned","2018-11-07T09:50:39Z"],["dc.date.available","2018-11-07T09:50:39Z"],["dc.date.issued","2015"],["dc.format.extent","211"],["dc.identifier.isi","364268800509"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/35748"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Karger"],["dc.publisher.place","Basel"],["dc.relation.issn","2296-5262"],["dc.relation.issn","2296-5270"],["dc.title","Wnt5a signaling mediates cell migration and invasion of Hodgkin Lymphoma in vitro and in xenograft models"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3637"],["dc.bibliographiccitation.issue","13"],["dc.bibliographiccitation.journal","Clinical Cancer Research"],["dc.bibliographiccitation.lastpage","3647"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Heemann, Christina"],["dc.contributor.author","Kreuz, Markus"],["dc.contributor.author","Stoller, Irene"],["dc.contributor.author","Schoof, Nils"],["dc.contributor.author","von Bonin, Frederike"],["dc.contributor.author","Ziepert, Marita"],["dc.contributor.author","Loeffler, Markus"],["dc.contributor.author","Jung, Wolfram"],["dc.contributor.author","Pfreundschuh, Michael"],["dc.contributor.author","Truemper, Lorenz H."],["dc.contributor.author","Kube, Dieter"],["dc.date.accessioned","2018-11-07T09:08:22Z"],["dc.date.available","2018-11-07T09:08:22Z"],["dc.date.issued","2012"],["dc.description.abstract","Purpose: Peripheral T-cell non-Hodgkin lymphomas (T-NHL) represent a small but heterogeneous and clinically aggressive subset of NHLs with a poor outcome. Cytokines or their receptors might be associated with the clinical outcome of these lymphomas. Therefore, we tested whether gene variations and serum levels of soluble TNF receptor (TNFR)I (sTNFRI), sTNFRII, interleukin (IL)-10, or sIL-4R are predictive for treatment response in T-NHLs. Experimental Design: Peripheral blood DNA from 117 patients with T-NHL treated in prospective clinical trials was subjected to genotyping analysis. Whenever possible, pretreatment sera were obtained, and circulating levels of sTNFRI, sTNFRII, IL-10, and sIL-4R were determined with a specific capture enzyme-linked immunoassay. Results: Patients characterized by TNFRI-609GG (rs4149570) showed a trend toward better event free survival [EFS; univariate: P = 0.041; multivariate: HR, 1.76; confidence interval (CI), 0.99-3.14 with P = 0.056]. A protective role of IL-10-1087A, -824T, and -597A reported in another study was not confirmed in our cohort. Patients with circulating levels of soluble TNFRII >= 2.16 ng/mL had a 2.07-fold increased relative risk for shorter overall survival (OS; univariate: P = 0.0034; multivariate: HR, 2.07; CI, 0.92-4.70 with P = 0.081) and a 2.49-fold higher risk for shorter EFS (univariate: P = 0.00068; multivariate: HR, 2.49; CI, 1.22-5.08 with P = 0.012). Elevations of circulating levels of sTNFRI, IL-10, and sIL-4R are frequent, but the clinical response in these patients is not significantly different. Conclusions: Our findings suggest a critical role for TNF-TNFR signaling for the clinical outcome of patients with peripheral T-NHLs. Clin Cancer Res; 18(13); 3637-47. (C)2012 AACR."],["dc.identifier.doi","10.1158/1078-0432.CCR-11-3299"],["dc.identifier.isi","000307502600016"],["dc.identifier.pmid","22573350"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/26018"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Cancer Research"],["dc.relation.issn","1078-0432"],["dc.title","Circulating Levels of TNF Receptor II Are Prognostic for Patients with Peripheral T-cell Non-Hodgkin Lymphoma"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","3"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Vascular Cell"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Becker, Jürgen"],["dc.contributor.author","Covelo-Fernandez, Ana"],["dc.contributor.author","von Bonin, Frederike"],["dc.contributor.author","Kube, Dieter"],["dc.contributor.author","Wilting, Jörg"],["dc.date.accessioned","2021-06-01T10:48:01Z"],["dc.date.available","2021-06-01T10:48:01Z"],["dc.date.issued","2012"],["dc.identifier.doi","10.1186/2045-824X-4-3"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7510"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85803"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","2045-824X"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Specific tumor-stroma interactions of EBV-positive Burkitt's lymphoma cells in the chick chorioallantoic membrane"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","43"],["dc.bibliographiccitation.journal","Cell Communication and Signaling"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Schrader, Alexandra"],["dc.contributor.author","Meyer, Katharina"],["dc.contributor.author","von Bonin, Frederike"],["dc.contributor.author","Vockerodt, Martina"],["dc.contributor.author","Walther, Neele"],["dc.contributor.author","Hand, Elisabeth"],["dc.contributor.author","Ulrich, Antje"],["dc.contributor.author","Matulewicz, Kamila"],["dc.contributor.author","Lenze, Dido"],["dc.contributor.author","Hummel, Michael"],["dc.contributor.author","Kieser, Arnd"],["dc.contributor.author","Engelke, Michael"],["dc.contributor.author","Truemper, Lorenz H."],["dc.contributor.author","Kube, Dieter"],["dc.date.accessioned","2018-11-07T09:02:13Z"],["dc.date.available","2018-11-07T09:02:13Z"],["dc.date.issued","2012"],["dc.description.abstract","Background: Aggressive Non-Hodgkin lymphomas (NHL) are a group of lymphomas derived from germinal centre B cells which display a heterogeneous pattern of oncogenic pathway activation. We postulate that specific immune response associated signalling, affecting gene transcription networks, may be associated with the activation of different oncogenic pathways in aggressive Non-Hodgkin lymphomas (NHL). Methodology: The B cell receptor (BCR), CD40, B-cell activating factor (BAFF)-receptors and Interleukin (IL) 21 receptor and Toll like receptor 4 (TLR4) were stimulated in human transformed germinal centre B cells by treatment with anti IgM F(ab)(2)-fragments, CD40L, BAFF, IL21 and LPS respectively. The changes in gene expression following the activation of Jak/STAT, NF-kappa B, MAPK, Ca2+ and PI3K signalling triggered by these stimuli was assessed using microarray analysis. The expression of top 100 genes which had a change in gene expression following stimulation was investigated in gene expression profiles of patients with Aggressive non-Hodgkin Lymphoma (NHL). Results: alpha IgM stimulation led to the largest number of changes in gene expression, affecting overall 6596 genes. While CD40L stimulation changed the expression of 1194 genes and IL21 stimulation affected 902 genes, only 283 and 129 genes were modulated by lipopolysaccharide or BAFF receptor stimulation, respectively. Interestingly, genes associated with a Burkitt-like phenotype, such as MYC, BCL6 or LEF1, were affected by alpha IgM. Unique and shared gene expression was delineated. NHL-patients were sorted according to their similarity in the expression of TOP100 affected genes to stimulated transformed germinal centre B cells The alpha IgM gene module discriminated individual DLBCL in a similar manner to CD40L or IL21 gene modules. DLBCLs with low module activation often carry chromosomal MYC aberrations. DLBCLs with high module activation show strong expression of genes involved in cell-cell communication, immune responses or negative feedback loops. Using chemical inhibitors for selected kinases we show that mitogen activated protein kinase-and phosphoinositide 3 kinase-signalling are dominantly involved in regulating genes included in the alpha IgM gene module. Conclusion: We provide an in vitro model system to investigate pathway activation in lymphomas. We defined the extent to which different immune response associated pathways are responsible for differences in gene expression which distinguish individual DLBCL cases. Our results support the view that tonic or constitutively active MAPK/ERK pathways are an important part of oncogenic signalling in NHL. The experimental model can now be applied to study the therapeutic potential of deregulated oncogenic pathways and to develop individual treatment strategies for lymphoma patients."],["dc.identifier.doi","10.1186/1478-811X-10-43"],["dc.identifier.isi","000314937400001"],["dc.identifier.pmid","23253402"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8528"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/24629"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1478-811X"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Global gene expression changes of in vitro stimulated human transformed germinal centre B cells as surrogate for oncogenic pathway activation in individual aggressive B cell lymphomas"],["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","586"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Genes and Immunity"],["dc.bibliographiccitation.lastpage","590"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Schoof, Nils"],["dc.contributor.author","von Bonin, Frederike"],["dc.contributor.author","Koenig, Inke R."],["dc.contributor.author","Moessner, R."],["dc.contributor.author","Krueger, Ulrich"],["dc.contributor.author","Reich, Kristian"],["dc.contributor.author","Berking, Carola"],["dc.contributor.author","Volkenandt, Matthias"],["dc.contributor.author","Ziegler, Andreas"],["dc.contributor.author","Boeckmann, L."],["dc.contributor.author","Kuschal, Christiane"],["dc.contributor.author","Thoms, K-M"],["dc.contributor.author","Kube, Dieter"],["dc.contributor.author","Emmert, Steffen"],["dc.date.accessioned","2018-11-07T11:24:52Z"],["dc.date.available","2018-11-07T11:24:52Z"],["dc.date.issued","2009"],["dc.description.abstract","Inherited promoter polymorphisms of the interleukin (IL)-10 gene resulting in altered IL-10 production may contribute to a genetic susceptibility for melanoma. We investigated the role of a haplotype from distal as well as proximal polymorphic sites [-7400InDel, -6752AT (rs6676671), -3538AT (rs1800890), -1087AG (rs1800896), -597AC (rs1800872)] of the IL-10 5'-flanking region in a hospital-based case-control study of 165 Caucasian patients with cutaneous melanoma from Germany in comparison with 162 healthy cancer-free Caucasian control participants from the same area matched by age. Using multivariate analysis for the number of nevi and skin type, the IL-10 'higher producing' haplotype ITAGC was found to be significantly associated with a reduced risk of developing melanoma ( adjusted P = 0.02). Although our findings need to be confirmed by independent and larger multicenter studies, we have described for the first time the association of distal gene variants of the IL-10 gene as an independent risk factor for melanoma. Genes and Immunity ( 2009) 10, 586-590; doi:10.1038/gene.2009.40; published online 21 May 2009"],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft DFG [GRK1034]"],["dc.identifier.doi","10.1038/gene.2009.40"],["dc.identifier.isi","000269493400005"],["dc.identifier.pmid","19458621"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/56507"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","1466-4879"],["dc.title","Distal and proximal interleukin (IL)-10 promoter polymorphisms associated with risk of cutaneous melanoma development: a case-control study"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Annals of Human Genetics"],["dc.bibliographiccitation.volume","76"],["dc.contributor.author","Viktorova, Elena"],["dc.contributor.author","Malzahn, Doerthe"],["dc.contributor.author","Balavarca, Yesilda"],["dc.contributor.author","Isernhagen, Antje"],["dc.contributor.author","von Bonin, Frederike"],["dc.contributor.author","Michael, Janne"],["dc.contributor.author","Wulf, Gerald"],["dc.contributor.author","Kube, Dieter"],["dc.contributor.author","Dressel, Ralf"],["dc.contributor.author","Bickeboeller, Heike"],["dc.date.accessioned","2018-11-07T09:06:11Z"],["dc.date.available","2018-11-07T09:06:11Z"],["dc.date.issued","2012"],["dc.format.extent","433"],["dc.identifier.isi","000307377000064"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/25495"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.publisher.place","Hoboken"],["dc.relation.conference","European Mathematical Genetics Meeting"],["dc.relation.eventlocation","Gottingen, GERMANY"],["dc.relation.issn","0003-4800"],["dc.title","Association of MICA-129 genotype with common risks of hematopoietic stem cell transplantation (HSCT)"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Experimental Dermatology"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Schoof, Nils"],["dc.contributor.author","von Bonin, Frederike"],["dc.contributor.author","Koenig, Inke R."],["dc.contributor.author","Moessner, R."],["dc.contributor.author","Krueger, Ulrich"],["dc.contributor.author","Reich, Kristian"],["dc.contributor.author","Ziegler, Andreas"],["dc.contributor.author","Boeckmann, L."],["dc.contributor.author","Kuschal, Christiane"],["dc.contributor.author","Thoms, Kai Martin"],["dc.contributor.author","Kube, Dieter"],["dc.contributor.author","Emmert, Steffen"],["dc.date.accessioned","2018-11-07T08:32:01Z"],["dc.date.available","2018-11-07T08:32:01Z"],["dc.date.issued","2009"],["dc.format.extent","284"],["dc.identifier.isi","000263520200070"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/17251"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell Publishing, Inc"],["dc.publisher.place","Malden"],["dc.relation.conference","36th Annual Meeting of the Arbeitsgemeinschaft-Dermatologishche-Forschung"],["dc.relation.eventlocation","Heidelberg, GERMANY"],["dc.relation.issn","0906-6705"],["dc.title","Distal and proximal interleukin-10 promoter polymorphisms associated with risk of cutaneous melanoma development: a case-control study"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","13"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Oncogene"],["dc.bibliographiccitation.lastpage","23"],["dc.bibliographiccitation.volume","36"],["dc.contributor.author","Linke, F."],["dc.contributor.author","Zaunig, S."],["dc.contributor.author","Nietert, M. M."],["dc.contributor.author","Bonin, F. von"],["dc.contributor.author","Lutz, S."],["dc.contributor.author","Dullin, C."],["dc.contributor.author","Janovská, P."],["dc.contributor.author","Beissbarth, T."],["dc.contributor.author","Alves, F."],["dc.contributor.author","Klapper, W."],["dc.contributor.author","Bryja, V."],["dc.contributor.author","Pukrop, T."],["dc.contributor.author","Trümper, L."],["dc.contributor.author","Wilting, J."],["dc.contributor.author","Kube, D."],["dc.date.accessioned","2018-10-19T06:32:50Z"],["dc.date.available","2018-10-19T06:32:50Z"],["dc.date.issued","2017"],["dc.description.abstract","Classical Hodgkin lymphoma (cHL) has a typical clinical manifestation, with dissemination involving functionally neighboring lymph nodes. The factors involved in the spread of lymphoma cells are poorly understood. Here we show that cHL cell lines migrate with higher rates compared with non-Hodgkin lymphoma cell lines. cHL cell migration, invasion and adhesion depend on autocrine WNT signaling as revealed by the inhibition of WNT secretion with the porcupine inhibitors Wnt-C59/IWP-2, but did not affect cell proliferation. While application of recombinant WNT5A or WNT5A overexpression stimulates HL cell migration, neither WNT10A, WNT10B nor WNT16 did so. Time-lapse studies revealed an amoeboid type of cell migration modulated by WNT5A. Reduced migration distances and velocity of cHL cells, as well as altered movement patterns, were observed using porcupine inhibitor or WNT5A antagonist. Knockdown of Frizzled5 and Dishevelled3 disrupted the WNT5A-mediated RHOA activation and cell migration. Overexpression of DVL3-K435M or inhibition of ROCK (Rho-associated protein kinase) by Y-27632/H1152P disrupted cHL cell migration. In addition to these mechanistic insights into the role of WNT5A in vitro, global gene expression data revealed an increased WNT5A expression in primary HL cells in comparison with normal B-cell subsets and other lymphomas. Furthermore, the activity of both porcupine and WNT5A in cHL cells had an impact on lymphoma development in the chick chorionallantoic membrane assay. Massive bleeding of these lymphomas was significantly reduced after inhibition of WNT secretion by Wnt-C59. Therefore, a model is proposed where WNT signaling has an important role in regulating tumor-promoting processes."],["dc.fs.pkfprnr","66887"],["dc.identifier.doi","10.1038/onc.2016.183"],["dc.identifier.fs","626468"],["dc.identifier.pmid","27270428"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/16088"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.eissn","1476-5594"],["dc.title","WNT5A: a motility-promoting factor in Hodgkin lymphoma"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]