Farhat, Katja

[["dc.bibliographiccitation.firstpage","33756"],["dc.bibliographiccitation.issue","44"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","33763"],["dc.bibliographiccitation.volume","285"],["dc.contributor.author","Vogel, Sabine"],["dc.contributor.author","Wottawa, Marieke"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Zieseniss, Anke"],["dc.contributor.author","Schnelle, Moritz"],["dc.contributor.author","Le-Huu, Sinja"],["dc.contributor.author","von Ahlen, Melanie"],["dc.contributor.author","Malz, Cordula R."],["dc.contributor.author","Camenisch, Gieri"],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.date.accessioned","2018-11-07T08:37:53Z"],["dc.date.available","2018-11-07T08:37:53Z"],["dc.date.issued","2010"],["dc.description.abstract","Cells are responding to hypoxia via prolyl-4-hydroxylase domain (PHD) enzymes, which are responsible for oxygen-dependent hydroxylation of the hypoxia-inducible factor (HIF)-1 alpha subunit. To gain further insight into PHD function, we generated knockdown cell models for the PHD2 isoform, which is the main isoform regulating HIF-1 alpha hydroxylation and thus stability in normoxia. Induction of a PHD2 knockdown in tetracycline-inducible HeLa PHD2 knockdown cells resulted in increased F-actin formation as detected by phalloidin staining. A similar effect could be observed in the stably transfected PHD2 knockdown cell clones 1B6 and 3B7. F-actin is at least in part responsible for shaping cell morphology as well as regulating cell migration. Cell migration was impaired significantly as a consequence of PHD2 knockdown in a scratch assay. Mechanistically, PHD2 knockdown resulted in activation of the RhoA (Ras homolog gene family member A)/Rho-associated kinase pathway with subsequent phosphorylation of cofilin. Because cofilin phosphorylation impairs its actin-severing function, this may explain the F-actin phenotype, thereby providing a functional link between PHD2-dependent signaling and cell motility."],["dc.identifier.doi","10.1074/jbc.M110.132985"],["dc.identifier.isi","000283354000021"],["dc.identifier.pmid","20801873"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6193"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18648"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Soc Biochemistry Molecular Biology Inc"],["dc.relation.issn","0021-9258"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Prolyl Hydroxylase Domain (PHD) 2 Affects Cell Migration and F-actin Formation via RhoA/Rho-associated Kinase-dependent Cofilin Phosphorylation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1331"],["dc.bibliographiccitation.issue","8"],["dc.bibliographiccitation.journal","Glia"],["dc.bibliographiccitation.lastpage","1346"],["dc.bibliographiccitation.volume","61"],["dc.contributor.author","Chuang, Han-Ning"],["dc.contributor.author","van Rossum, Denise"],["dc.contributor.author","Sieger, Dirk"],["dc.contributor.author","Siam, Laila"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Bayerlova, Michaela"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Scheffel, Joerg"],["dc.contributor.author","Schulz, Matthias"],["dc.contributor.author","Dehghani, Faramarz"],["dc.contributor.author","Stadelmann, Christine"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Pukrop, Tobias"],["dc.date.accessioned","2018-11-07T09:21:57Z"],["dc.date.available","2018-11-07T09:21:57Z"],["dc.date.issued","2013"],["dc.description.abstract","The metastatic colonization of the brain by carcinoma cells is still barely understood, in particular when considering interactions with the host tissue. The colonization comes with a substantial destruction of the surrounding host tissue. This leads to activation of damage responses by resident innate immune cells to protect, repair, and organize the wound healing, but may distract from tumoricidal actions. We recently demonstrated that microglia, innate immune cells of the CNS, assist carcinoma cell invasion. Here we report that this is a fatal side effect of a physiological damage response of the brain tissue. In a brain slice coculture model, contact with both benign and malignant epithelial cells induced a response by microglia and astrocytes comparable to that seen at the interface of human cerebral metastases. While the glial damage response intended to protect the brain from intrusion of benign epithelial cells by inducing apoptosis, it proved ineffective against various malignant cell types. They did not undergo apoptosis and actually exploited the local tissue reaction to invade instead. Gene expression and functional analyses revealed that the C-X-C chemokine receptor type 4 (CXCR4) and WNT signaling were involved in this process. Furthermore, CXCR4-regulated microglia were recruited to sites of brain injury in a zebrafish model and CXCR4 was expressed in human stroke patients, suggesting a conserved role in damage responses to various types of brain injuries. Together, our findings point to a detrimental misuse of the glial damage response program by carcinoma cells resistant to glia-induced apoptosis. GLIA 2013;61:1331-1346"],["dc.identifier.doi","10.1002/glia.22518"],["dc.identifier.isi","000321983400011"],["dc.identifier.pmid","23832647"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10955"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29226"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","0894-1491"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Carcinoma cells misuse the host tissue damage response to invade the brain"],["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.artnumber","e18605"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Deng, Ying"],["dc.contributor.author","Zhang, W."],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Oberland, Sonja"],["dc.contributor.author","Gisselmann, Guenter"],["dc.contributor.author","Neuhaus, Eva M."],["dc.date.accessioned","2018-11-07T08:57:06Z"],["dc.date.available","2018-11-07T08:57:06Z"],["dc.date.issued","2011"],["dc.description.abstract","Seven-transmembrane receptors typically mediate olfactory signal transduction by coupling to G-proteins. Although insect odorant receptors have seven transmembrane domains like G-protein coupled receptors, they have an inverted membrane topology, constituting a key difference between the olfactory systems of insects and other animals. While heteromeric insect ORs form ligand-activated non-selective cation channels in recombinant expression systems, the evidence for an involvement of cyclic nucleotides and G-proteins in odor reception is inconsistent. We addressed this question in vivo by analyzing the role of G-proteins in olfactory signaling using electrophysiological recordings. We found that G alpha(s) plays a crucial role for odorant induced signal transduction in OR83b expressing olfactory sensory neurons, but not in neurons expressing CO2 responsive proteins GR21a/GR63a. Moreover, signaling of Drosophila ORs involved G alpha(s) also in a heterologous expression system. In agreement with these observations was the finding that elevated levels of cAMP result in increased firing rates, demonstrating the existence of a cAMP dependent excitatory signaling pathway in the sensory neurons. Together, we provide evidence that G alpha(s) plays a role in the OR mediated signaling cascade in Drosophila."],["dc.description.sponsorship","NE [755/3-1]; Max-Planck-Research School for Chemical Biology (IMPRS-CB)"],["dc.identifier.doi","10.1371/journal.pone.0018605"],["dc.identifier.isi","000289238700028"],["dc.identifier.pmid","21490930"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/8314"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/23308"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 2.5"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.5"],["dc.title","The Stimulatory G alpha(s) Protein Is Involved in Olfactory Signal Transduction in Drosophila"],["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.artnumber","e69128"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","PLoS ONE"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Vogler, Melanie"],["dc.contributor.author","Vogel, Sabine"],["dc.contributor.author","Krull, Sabine"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Leisering, Pia"],["dc.contributor.author","Lutz, Susanne"],["dc.contributor.author","Wuertz, Christina M."],["dc.contributor.author","Katschinski, Doerthe Magdalena"],["dc.contributor.author","Zieseniss, Anke"],["dc.date.accessioned","2018-11-07T09:22:20Z"],["dc.date.available","2018-11-07T09:22:20Z"],["dc.date.issued","2013"],["dc.description.abstract","Cells can adapt to hypoxia by various mechanisms. Yet, hypoxia-induced effects on the cytoskeleton-based cell architecture and functions are largely unknown. Here we present a comprehensive analysis of the architecture and function of L929 fibroblasts under hypoxic conditions (1% O-2). Cells cultivated in hypoxia showed striking morphological differences as compared to cells cultivated under normoxic conditions (20% O-2). These changes include an enlargement of cell area and volume, increased numbers of focal contacts and loss of cell polarization. Furthermore the beta- and gamma-actin distribution is greatly altered. These hypoxic adjustments are associated with enhanced cell spreading and a decline of cell motility in wound closure and single cell motility assays. As the hypoxia-inducible factor-1 alpha (HIF-1 alpha) is stabilised in hypoxia and plays a pivotal role in the transcriptional response to changes in oxygen availability we used an shRNA-approach to examine the role of HIF-1 alpha in cytoskeleton-related architecture and functions. We show that the observed increase in cell area, actin filament rearrangement, decrease of single cell migration in hypoxia and the maintenance of p-cofilin levels is dependent on HIF-1 alpha stabilisation."],["dc.identifier.doi","10.1371/journal.pone.0069128"],["dc.identifier.isi","000324146200061"],["dc.identifier.pmid","23874890"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9965"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/29319"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Public Library Science"],["dc.relation.issn","1932-6203"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Hypoxia Modulates Fibroblastic Architecture, Adhesion and Migration: A Role for HIF-1 alpha in Cofilin Regulation and Cytoplasmic Actin Distribution"],["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","107"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Cell and tissue research"],["dc.bibliographiccitation.lastpage","120"],["dc.bibliographiccitation.volume","343"],["dc.contributor.author","Jungi, Thomas W"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Burgener, Iwan A"],["dc.contributor.author","Werling, Dirk"],["dc.date.accessioned","2019-07-09T11:53:48Z"],["dc.date.available","2019-07-09T11:53:48Z"],["dc.date.issued","2011"],["dc.description.abstract","Toll-like receptors are pattern recognition receptors with which hosts recognize pathogen-associated molecular patterns (PAMP). This recognition process is translated rapidly into a meaningful defense reaction. This form of innate host defense is preserved in the animal kingdom: invertebrates heavily depend on it; higher vertebrates also have an adaptive immune system. Both adaptive and innate immune systems are intertwined in that the former also depends on an intact innate recognition and response system. Members of the TLR system cover recognition of parasitic, bacterial or viral germs. Due to the constraints imposed by the necessity to recognize PAMP and to interact with downstream signaling molecules, the TLR system is relatively conserved in evolution. Nevertheless, subtle species differences have been reported for several mammalian TLR members. Examples of this will be given. In all mammalian species investigated, part of the coding sequence is available for the most important TLR members, thus allowing study of expression of these TLR members in various tissues by reverse-transcription polymerase chain reaction in its classical (RT-PCR) and quantitative real time RT-PCR (qRT-PCR) form. In some species, the whole coding sequences of the most important or even all TLR members are known. This allows construction of cDNA and transfection of common host cells, thus permitting functional studies. Extensive investigations were devoted to the study of non-synonymous single nucleotide polymorphisms. In a few cases, expression of a given amino acid in the extracellular (ligand-binding) portion of TLR members could be associated with infectious diseases. This will be discussed below."],["dc.identifier.doi","10.1007/s00441-010-1047-8"],["dc.identifier.fs","584201"],["dc.identifier.pmid","20927536"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60498"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1432-0878"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.mesh","Animal Diseases"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Animals, Domestic"],["dc.subject.mesh","Bacteria"],["dc.subject.mesh","Signal Transduction"],["dc.subject.mesh","Species Specificity"],["dc.subject.mesh","Toll-Like Receptors"],["dc.title","Toll-like receptors in domestic animals."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","34"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Veterinary research"],["dc.bibliographiccitation.lastpage","34"],["dc.bibliographiccitation.volume","41"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Riekenberg, Sabine"],["dc.contributor.author","Jung, Günther"],["dc.contributor.author","Wiesmüller, Karl-Heinz"],["dc.contributor.author","Jungi, Thomas W."],["dc.contributor.author","Ulmer, Artur J."],["dc.date.accessioned","2019-07-09T11:53:04Z"],["dc.date.available","2019-07-09T11:53:04Z"],["dc.date.issued","2010"],["dc.description.abstract","Toll-like receptors (TLR) are highly conserved pattern recognition receptors of the innate immune system. Toll-like receptor 2 (TLR2) recognizes bacterial lipopeptides in a heterodimeric complex with TLR6 or TLR1, thereby discriminating between di- or triacylated lipopeptides, respectively. Previously, we found that HEK293 cells transfected with bovine TLR2 (boTLR2) were able to respond to diacylated lipopeptides but did not recognize triacylated lipopeptides, even after cotransfection with the so far published sequence of boTLR1. In this study we now could show that primary bovine cells were in general able to detect triacylated lipopetides. A closer investigation of the boTLR1 gene locus revealed an additional ATG 195 base pairs upstream from the published start codon. Its transcription would result in an N-terminus with high identity to human and murine TLR1 (huTLR1, muTLR1). Cloning and cotransfection of this longer boTLR1 with boTLR2 now resulted in the recognition of triacylated lipopeptides by HEK293 cells, thereby resembling the ex vivo observation. Analysis of the structure-activity relationship showed that the ester-bound acid chains of these lipopeptides need to consist of at least 12 carbon atoms to activate the bovine heterodimer showing similarity to the recognition by huTLR2/huTLR1. In contrast, HEK293 cell cotransfected with muTLR2 and muTLR1 could already be activated by lipopeptides with shorter fatty acids of only 6 carbon atoms. Thus, our data indicate that the additional N-terminal nucleotides belong to the full length and functionally active boTLR1 (boTLR1-fl) which participates in a species-specific recognition of bacterial lipopeptides."],["dc.identifier.doi","10.1051/vetres/2010006"],["dc.identifier.fs","576969"],["dc.identifier.pmid","20167196"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6864"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60334"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","0928-4249"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.subject.ddc","610"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Cattle"],["dc.subject.mesh","Cell Line"],["dc.subject.mesh","Gene Expression Regulation"],["dc.subject.mesh","Humans"],["dc.subject.mesh","Lipopeptides"],["dc.subject.mesh","Mice"],["dc.subject.mesh","Toll-Like Receptor 1"],["dc.subject.mesh","Toll-Like Receptor 2"],["dc.title","Identification of full length bovine TLR1 and functional characterization of lipopeptide recognition by bovine TLR2/1 heterodimer."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1449"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","1460"],["dc.bibliographiccitation.volume","4"],["dc.contributor.author","Rietkötter, Eva"],["dc.contributor.author","Menck, Kerstin"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Farhat, Katja"],["dc.contributor.author","Schaffrinski, Meike"],["dc.contributor.author","Schulz, Matthias"],["dc.contributor.author","Hanisch, Uwe-Karsten"],["dc.contributor.author","Binder, Claudia"],["dc.contributor.author","Pukrop, Tobias"],["dc.date.accessioned","2019-07-10T08:11:45Z"],["dc.date.available","2019-07-10T08:11:45Z"],["dc.date.issued","2013-09-01"],["dc.description.abstract","The bisphosphonate zoledronic acid (ZA) significantly reduces complications of bone metastasis by inhibiting resident macrophages, the osteoclasts. Recent clinical trials indicate additional anti-metastatic effects of ZA outside the bone. However, which step of metastasis is influenced and whether thisis due to directtoxicity on cancer cells or inhibition of the tumor promoting microenvironment, is unknown. In particular, tumor-associated and resident macrophages support each step of organ metastasis and could be a crucial target of ZA. Thus, we comparatively investigate the ZA effects on: i) different types of macrophages, ii) on breast cancer cells but also iii) on macrophage-induced invasion. We demonstrate that ZA concentrations reflecting the plasma level affected viability of human macrophages, murine bone marrow-derived macrophages as well as their resident brain equivalents, the microglia, while it did not influence the tested cancer cells. However, the effects on the macrophages subsequently reduced the macrophage/microglia-induced invasiveness of the cancer cells. In line with this, manipulation of microglia by ZA in organotypic brain slice cocultures reduced the tissue invasion by carcinoma cells. The characterization of human macrophages after ZA treatment revealed a phenotype/response shift, in particular after external stimulation. In conclusion, we show that therapeutic concentrations of ZA affect all types of macrophages but not the cancer cells. Thus, anti-metastatic effects of ZA are predominantly caused by modulating the microenvironment. Most importantly, our findings demonstrate that ZA reduced microglia-assisted invasion of cancer cells to the brain tissue, indicating a potential therapeutic role in the prevention of cerebral metastasis."],["dc.identifier.fs","599082"],["dc.identifier.pmid","24036536"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/10758"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/60792"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1949-2553"],["dc.relation.orgunit","Universitätsmedizin Göttingen"],["dc.rights","CC BY 3.0"],["dc.rights.uri","http://creativecommons.org/licenses/by/3.0"],["dc.subject.mesh","Animals"],["dc.subject.mesh","Breast Neoplasms"],["dc.subject.mesh","Cell Communication"],["dc.subject.mesh","Cell Line, Tumor"],["dc.subject.mesh","Cell Proliferation"],["dc.subject.mesh","Coculture Techniques"],["dc.subject.mesh","Diphosphonates"],["dc.subject.mesh","Female"],["dc.subject.mesh","Humans"],["dc.subject.mesh","Imidazoles"],["dc.subject.mesh","MCF-7 Cells"],["dc.subject.mesh","Macrophages"],["dc.subject.mesh","Matrix Metalloproteinases"],["dc.subject.mesh","Mice"],["dc.subject.mesh","Microglia"],["dc.subject.mesh","Tumor Microenvironment"],["dc.title","Zoledronic acid inhibits macrophage/microglia-assisted breast cancer cell invasion."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]