Wegwitz, Florian

[["dc.bibliographiccitation.firstpage","8959"],["dc.bibliographiccitation.issue","16"],["dc.bibliographiccitation.journal","Nucleic Acids Research"],["dc.bibliographiccitation.lastpage","8976"],["dc.bibliographiccitation.volume","48"],["dc.contributor.author","Wüst, Hannah M"],["dc.contributor.author","Wegener, Amélie"],["dc.contributor.author","Fröb, Franziska"],["dc.contributor.author","Hartwig, Anna C"],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Kari, Vijayalakshmi"],["dc.contributor.author","Schimmel, Margit"],["dc.contributor.author","Tamm, Ernst R"],["dc.contributor.author","Johnsen, Steven A"],["dc.contributor.author","Wegner, Michael"],["dc.contributor.author","Sock, Elisabeth"],["dc.date.accessioned","2021-04-14T08:22:59Z"],["dc.date.available","2021-04-14T08:22:59Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1093/nar/gkaa606"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/80763"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1362-4962"],["dc.relation.issn","0305-1048"],["dc.title","Egr2-guided histone H2B monoubiquitination is required for peripheral nervous system myelination"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","37906"],["dc.bibliographiccitation.issue","35"],["dc.bibliographiccitation.journal","Oncotarget"],["dc.bibliographiccitation.lastpage","37918"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Kosinsky, Robyn L."],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Hellbach, Nicole"],["dc.contributor.author","Dobbelstein, Matthias"],["dc.contributor.author","Mansouri, Ahmed"],["dc.contributor.author","Vogel, Tanja"],["dc.contributor.author","Begus-Nahrmann, Yvonne"],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2019-07-09T11:42:03Z"],["dc.date.available","2019-07-09T11:42:03Z"],["dc.date.issued","2015-11-10"],["dc.description.abstract","Epigenetic regulatory mechanisms play a central role in controlling gene expression during development, cell differentiation and tumorigenesis. Monoubiquitination of histone H2B is one epigenetic modification which is dynamically regulated by the opposing activities of specific ubiquitin ligases and deubiquitinating enzymes (DUBs). The Ubiquitin-specific Protease 22 (USP22) is the ubiquitin hydrolase component of the human SAGA complex which deubiquitinates histone H2B during transcription. Recently, many studies have investigated an oncogenic potential of USP22 overexpression. However, its physiological function in organ maintenance, development and its cellular function remain largely unknown. A previous study reported embryonic lethality in Usp22 knockout mice. Here we describe a mouse model with a global reduction of USP22 levels which expresses the LacZ gene under the control of the endogenous Usp22 promoter. Using this reporter we found Usp22 to be ubiquitously expressed in murine embryos. Notably, adult Usp22lacZ/lacZ displayed low residual Usp22 expression levels coupled with a reduced body size and weight. Interestingly, the reduction of Usp22 significantly influenced the frequency of differentiated cells in the small intestine and the brain while H2B and H2Bub1 levels remained constant. Taken together, we provide evidence for a physiological role for USP22 in controlling cell differentiation and lineage specification."],["dc.identifier.doi","10.18632/oncotarget.5412"],["dc.identifier.pmid","26431380"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/12736"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/58576"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.relation.issn","1949-2553"],["dc.rights","CC BY 3.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/3.0"],["dc.title","Usp22 deficiency impairs intestinal epithelial lineage specification in vivo."],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","7"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Clinical Epigenetics"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Pantelaiou-Prokaki, Garyfallia"],["dc.contributor.author","Mieczkowska, Iga"],["dc.contributor.author","Schmidt, Geske E."],["dc.contributor.author","Fritzsche, Sonja"],["dc.contributor.author","Prokakis, Evangelos"],["dc.contributor.author","Gallwas, Julia"],["dc.contributor.author","Wegwitz, Florian"],["dc.date.accessioned","2022-02-01T10:31:32Z"],["dc.date.accessioned","2022-08-18T12:33:13Z"],["dc.date.available","2022-02-01T10:31:32Z"],["dc.date.available","2022-08-18T12:33:13Z"],["dc.date.issued","2022-01-11"],["dc.date.updated","2022-07-29T12:00:15Z"],["dc.description.abstract","Background Basal-like breast cancer (BLBC) is one of the most aggressive malignant diseases in women with an increased metastatic behavior and poor prognosis compared to other molecular subtypes of breast cancer. Resistance to chemotherapy is the main cause of treatment failure in BLBC. Therefore, novel therapeutic strategies counteracting the gain of aggressiveness underlying therapy resistance are urgently needed. The epithelial-to-mesenchymal transition (EMT) has been established as one central process stimulating cancer cell migratory capacity but also acquisition of chemotherapy-resistant properties. In this study, we aimed to uncover epigenetic factors involved in the EMT-transcriptional program occurring in BLBC cells surviving conventional chemotherapy. Results Using whole transcriptome data from a murine mammary carcinoma cell line (pG-2), we identified upregulation of Hdac4 , 7 and 8 in tumor cells surviving conventional chemotherapy. Subsequent analyses of human BLBC patient datasets and cell lines established HDAC8 as the most promising factor sustaining tumor cell viability. ChIP-sequencing data analysis identified a pronounced loss of H3K27ac at regulatory regions of master transcription factors (TFs) of epithelial phenotype like Gata3 , Elf5 , Rora and Grhl2 upon chemotherapy. Interestingly, impairment of HDAC8 activity reverted epithelial-TFs levels. Furthermore, loss of HDAC8 activity sensitized tumor cells to chemotherapeutic treatments, even at low doses. Conclusion The current study reveals a previously unknown transcriptional repressive function of HDAC8 exerted on a panel of transcription factors involved in the maintenance of epithelial cell phenotype, thereby supporting BLBC cell survival to conventional chemotherapy. Our data establish HDAC8 as an attractive therapeutically targetable epigenetic factor to increase the efficiency of chemotherapeutics. Graphical abstract"],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.citation","Clinical Epigenetics. 2022 Jan 11;14(1):7"],["dc.identifier.doi","10.1186/s13148-022-01228-4"],["dc.identifier.pii","1228"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/98885"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112916"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-517"],["dc.publisher","BioMed Central"],["dc.relation.eissn","1868-7083"],["dc.relation.issn","1868-7075"],["dc.rights","CC BY 4.0"],["dc.rights.holder","The Author(s)"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.subject","HDAC8"],["dc.subject","MET"],["dc.subject","EMT"],["dc.subject","BLBC"],["dc.subject","TNBC"],["dc.subject","Chemotherapy"],["dc.subject","Epigenetics"],["dc.subject","H3K27ac"],["dc.subject","Epithelial transcription factors"],["dc.title","HDAC8 suppresses the epithelial phenotype and promotes EMT in chemotherapy-treated basal-like breast cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","6334"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Nucleic Acids Research"],["dc.bibliographiccitation.lastpage","6349"],["dc.bibliographiccitation.volume","45"],["dc.contributor.author","Mishra, Vivek Kumar"],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Kosinsky, Robyn Laura"],["dc.contributor.author","Sen, Madhobi"],["dc.contributor.author","Baumgartner, Roland"],["dc.contributor.author","Wulff, Tanja"],["dc.contributor.author","Siveke, Jens T."],["dc.contributor.author","Schildhaus, Hans-Ulrich"],["dc.contributor.author","Najafova, Zeynab"],["dc.contributor.author","Kari, Vijayalakshmi"],["dc.contributor.author","Kohlhof, Hella"],["dc.contributor.author","Hessmann, Elisabeth"],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2018-11-07T10:22:37Z"],["dc.date.available","2018-11-07T10:22:37Z"],["dc.date.issued","2017"],["dc.description.abstract","Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive cancer with a particularly dismal prognosis. Histone deacetylases (HDAC) are epigenetic modulators whose activity is frequently deregulated in various cancers including PDAC. In particular, class-I HDACs (HDAC 1, 2, 3 and 8) have been shown to play an important role in PDAC. In this study, we investigated the effects of the class Ispecific HDAC inhibitor (HDACi) 4SC-202 in multiple PDAC cell lines in promoting tumor cell differentiation. We show that 4SC-202 negatively affects TGF beta signaling and inhibits TGF beta-induced epithelial-tomesenchymal transition (EMT). Moreover, 4SC-202 markedly induced p21 (CDKN1A) expression and significantly attenuated cell proliferation. Mechanistically, genome-wide studies revealed that 4SC-202-induced genes were enriched for Bromodomain-containing Protein-4 (BRD4) and MYC occupancy. BRD4, a well-characterized acetyllysine reader, has been shown to play a major role in regulating transcription of selected subsets of genes. Importantly, BRD4 and MYC are essential for the expression of a subgroup of genes induced by class-I HDACi. Taken together, our study uncovers a previously unknown role of BRD4 and MYC in eliciting the HDACi-mediated induction of a subset of genes and provides molecular insight into the mechanisms of HDACi action in PDAC."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2017"],["dc.identifier.doi","10.1093/nar/gkx212"],["dc.identifier.isi","000403693000023"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14605"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/42309"],["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","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Histone deacetylase class-I inhibition promotes epithelial gene expression in pancreatic cancer cells in a BRD4-and MYC-dependent manner"],["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.journal","Cancer Research"],["dc.bibliographiccitation.volume","76"],["dc.contributor.author","Mishra, Vivek Kumar"],["dc.contributor.author","Kari, Vijayalakshmi"],["dc.contributor.author","Subramaniam, Malayannan"],["dc.contributor.author","Baumgart, Simon J."],["dc.contributor.author","Nagarajan, Sankari"],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Spelsberg, Thomas C."],["dc.contributor.author","Hawse, John R."],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2018-11-07T10:19:22Z"],["dc.date.available","2018-11-07T10:19:22Z"],["dc.date.issued","2016"],["dc.identifier.doi","10.1158/1538-7445.CHROMEPI15-A03"],["dc.identifier.isi","000368930800003"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/41642"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Amer Assoc Cancer Research"],["dc.publisher.place","Philadelphia"],["dc.relation.conference","American-Association-for-Cancer-Research (AACR) Special Conference on Chromatin and Epigenetics in Cancer"],["dc.relation.eventlocation","Atlanta, GA"],["dc.relation.issn","1538-7445"],["dc.relation.issn","0008-5472"],["dc.title","Kruppel-like Transcription Factor-10 (KLF10) suppresses the TGF beta-induced epithelial-to-mesenchymal transition"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","E521"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","International Journal of Cancer"],["dc.bibliographiccitation.lastpage","E533"],["dc.bibliographiccitation.volume","136"],["dc.contributor.author","Lenfert, Eva"],["dc.contributor.author","Maenz, Claudia"],["dc.contributor.author","Heinlein, Christina"],["dc.contributor.author","Jannasch, Katharina"],["dc.contributor.author","Schumacher, Udo"],["dc.contributor.author","Pantel, Klaus"],["dc.contributor.author","Tolstonog, Genrich V."],["dc.contributor.author","Deppert, Wolfgang R."],["dc.contributor.author","Wegwitz, Florian"],["dc.date.accessioned","2018-11-07T09:59:40Z"],["dc.date.available","2018-11-07T09:59:40Z"],["dc.date.issued","2015"],["dc.description.abstract","To study the postulated mutant p53 (mutp53) gain of function effects in mammary tumor development, progression and metastasis, we crossed SV40 transgenic WAP-T mice with mutant p53 transgenic WAP-mutp53 mice. Compared to tumors in monotransgenic WAP-T mice, tumors in bitransgenic WAP-T x WAP-mutp53 mice showed higher tumor grading, enhanced vascularization, and significantly increased metastasis. Bitransgenic tumors revealed a gene signature associated with the oncogenic epithelial-mesenchymal transition pathway (EMT gene signature). In cultures of WAP-T tumor-derived G-2 cancer cells, which are comprised of subpopulations displaying mesenchymal and epithelial phenotypes, this EMT gene signature was associated with the mesenchymal compartment. Furthermore, ectopic expression of mutp53 in G-2 cells sufficed to induce a strong EMT phenotype. In contrast to these in vitro effects, monotransgenic and bitransgenic tumors were phenotypically similar suggesting that in vivo the tumor cell phenotype might be under control of the tumor microenvironment. In support, orthotopic transplantation of G-2 cells as well as of G-2 cells expressing ectopic mutp53 into syngeneic mice resulted in tumors with a predominantly epithelial phenotype, closely similar to that of endogenous primary tumors. We conclude that induction of an EMT gene signature by mutp53 in bitransgenic tumors primarily promotes tumor cell plasticity, that is, the probability of tumor cells to undergo EMT processes under appropriate stimuli, thereby possibly increasing their potential to disseminate and metastasize. What's new? Despite the loss of transcriptional activity, mutant p53 (mutp53) proteins display gain of function properties, such as the ability to contribute to tumor progression. To elucidate functional gains, the present study explored the effects of mutp53 expression in monotransgenic WAP-T mice and bitransgenic WAP-T x WAP-mutp53 mice. Mammary tumors from both models were phenotypically similar and possessed an epithelial-mesenchymal transition (EMT) gene signature associated with tumor cell plasticity. However, mammary tumors in bitransgenic mice showed enhanced metastatic potential. Additional findings from in vitro experiments indicate that the tumor microenvironment plays a key role in regulating tumor cell phenotype and invasiveness."],["dc.identifier.doi","10.1002/ijc.29186"],["dc.identifier.isi","000347705200005"],["dc.identifier.pmid","25195563"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/37647"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.relation.issn","1097-0215"],["dc.relation.issn","0020-7136"],["dc.title","Mutant p53 promotes epithelial-mesenchymal plasticity and enhances metastasis in mammary carcinomas of WAP-T mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2616"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Cells"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Kolb, Katharina"],["dc.contributor.author","Hellinger, Johanna"],["dc.contributor.author","Kansy, Maike"],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Bauerschmitz, Gerd"],["dc.contributor.author","Emons, Günter"],["dc.contributor.author","Gründker, Carsten"],["dc.date.accessioned","2021-04-14T08:26:32Z"],["dc.date.available","2021-04-14T08:26:32Z"],["dc.date.issued","2020"],["dc.description.sponsorship","Deutsche Krebshilfe"],["dc.identifier.doi","10.3390/cells9122616"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81981"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.publisher","MDPI"],["dc.relation.eissn","2073-4409"],["dc.rights","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Influence of ARHGAP29 on the Invasion of Mesenchymal-Transformed Breast Cancer Cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","5885"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Anticancer Research"],["dc.bibliographiccitation.lastpage","5886"],["dc.bibliographiccitation.volume","34"],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Lenfert, Eva"],["dc.contributor.author","Maenz, Claudia"],["dc.contributor.author","Tolstonog, Genrich V."],["dc.contributor.author","Deppert, Wolfgang R."],["dc.date.accessioned","2018-11-07T09:34:27Z"],["dc.date.available","2018-11-07T09:34:27Z"],["dc.date.issued","2014"],["dc.identifier.isi","000343139500220"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/32173"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Int Inst Anticancer Research"],["dc.publisher.place","Athens"],["dc.relation.issn","1791-7530"],["dc.relation.issn","0250-7005"],["dc.title","WAP-T MICE: A PRECLINICAL MOUSE MODEL TO STUDY MAMMARY CARCINOGENESIS, PROGRESSION, AND METASTASIS"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Cell Death & Disease"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Kosinsky, Robyn Laura"],["dc.contributor.author","Helms, Marlena"],["dc.contributor.author","Zerche, Maria"],["dc.contributor.author","Wohn, Luisa"],["dc.contributor.author","Dyas, Anna"],["dc.contributor.author","Prokakis, Evangelos"],["dc.contributor.author","Kazerouni, Zahra Basir"],["dc.contributor.author","Bedi, Upasana"],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Johnsen, Steven A."],["dc.date.accessioned","2020-12-10T18:09:43Z"],["dc.date.available","2020-12-10T18:09:43Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1038/s41419-019-2141-9"],["dc.identifier.eissn","2041-4889"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17081"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/73737"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","USP22-dependent HSP90AB1 expression promotes resistance to HSP90 inhibition in mammary and colorectal cancer"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","959"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","Cells"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Hoen, Laura"],["dc.contributor.author","Rudisch, Christoph"],["dc.contributor.author","Wick, Michael"],["dc.contributor.author","Indenbirken, Daniela"],["dc.contributor.author","Grundhoff, Adam"],["dc.contributor.author","Wegwitz, Florian"],["dc.contributor.author","Kalkhof, Stefan"],["dc.contributor.author","Hildebrand, Janosch"],["dc.date.accessioned","2022-04-01T10:02:05Z"],["dc.date.available","2022-04-01T10:02:05Z"],["dc.date.issued","2022"],["dc.description.abstract","The human skin and in particular its outermost layer, the epidermis, protects the body from potentially harmful substances, radiation as well as excessive water loss. However, the interference between the various stress responses of the epidermal keratinocytes, which often occur simultaneously, is largely unknown. The focus of this study was to investigate the interference between osmotic stress and DNA damage response. In addition to revealing the already well-described regulation of diverse gene sets, for example, cellular processes such as transcription, translation, and metabolic pathways (e.g., the KEGG citrate cycle and Reactome G2/M checkpoints), gene expression analysis of osmotically stressed keratinocytes revealed an influence on the transcription of genes also related to UV-induced DNA damage response. A gene network regulating the H2AX phosphorylation was identified to be regulated by osmotic stress. To analyze and test the interference between osmotic stress and DNA damage response, which can be triggered by UV stress on the one hand and oxidative stress on the other, in more detail, primary human keratinocytes were cultured under osmotic stress conditions and subsequently exposed to UV light and H2O2, respectively. γH2AX measurements revealed lower γH2AX levels in cells previously cultured under osmotic stress conditions."],["dc.identifier.doi","10.3390/cells11060959"],["dc.identifier.pii","cells11060959"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/105819"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-530"],["dc.relation.eissn","2073-4409"],["dc.title","Osmotic Stress Interferes with DNA Damage Response and H2AX Phosphorylation in Human Keratinocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]