Bocuk, Derya

[["dc.bibliographiccitation.firstpage","342"],["dc.bibliographiccitation.journal","BMC Cancer"],["dc.bibliographiccitation.volume","17"],["dc.contributor.author","Bocuk, Derya"],["dc.contributor.author","Wolff, Alexander"],["dc.contributor.author","Krause, Petra"],["dc.contributor.author","Salinas, Gabriella"],["dc.contributor.author","Bleckmann, Annalen"],["dc.contributor.author","Hackl, Christina"],["dc.contributor.author","Beißbarth, Tim"],["dc.contributor.author","Koenig, Sarah"],["dc.date.accessioned","2018-10-10T10:45:50Z"],["dc.date.available","2018-10-10T10:45:50Z"],["dc.date.issued","2017"],["dc.description.abstract","Colorectal cancer (CRC) is the second leading cause of cancer-related death in men and women. Systemic disease with metastatic spread to distant sites such as the liver reduces the survival rate considerably. The aim of this study was to investigate the changes in gene expression that occur on invasion and expansion of CRC cells when forming metastases in the liver. The livers of syngeneic C57BL/6NCrl mice were inoculated with 1 million CRC cells (CMT-93) via the portal vein, leading to the stable formation of metastases within 4 weeks. RNA sequencing performed on the Illumina platform was employed to evaluate the expression profiles of more than 14,000 genes, utilizing the RNA of the cell line cells and liver metastases as well as from corresponding tumour-free liver. A total of 3329 differentially expressed genes (DEGs) were identified when cultured CMT-93 cells propagated as metastases in the liver. Hierarchical clustering on heat maps demonstrated the clear changes in gene expression of CMT-93 cells on propagation in the liver. Gene ontology analysis determined inflammation, angiogenesis, and signal transduction as the top three relevant biological processes involved. Using a selection list, matrix metallopeptidases 2, 7, and 9, wnt inhibitory factor, and chemokine receptor 4 were the top five significantly dysregulated genes. Bioinformatics assists in elucidating the factors and processes involved in CRC liver metastasis. Our results support the notion of an invasion-metastasis cascade involving CRC cells forming metastases on successful invasion and expansion within the liver. Furthermore, we identified a gene expression signature correlating strongly with invasiveness and migration. Our findings may guide future research on novel therapeutic targets in the treatment of CRC liver metastasis."],["dc.identifier.doi","10.1186/s12885-017-3342-1"],["dc.identifier.gro","630797"],["dc.identifier.pmid","28525976"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14459"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/15943"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.eissn","1471-2407"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","The adaptation of colorectal cancer cells when forming metastases in the liver: expression of associated genes and pathways in a mouse model"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","193"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Journal of Surgical Research"],["dc.bibliographiccitation.lastpage","205"],["dc.bibliographiccitation.volume","203"],["dc.contributor.author","Monin, Malte B."],["dc.contributor.author","Krause, Petra"],["dc.contributor.author","Stelling, Robin"],["dc.contributor.author","Bocuk, Derya"],["dc.contributor.author","Niebert, Sabine"],["dc.contributor.author","Klemm, Florian"],["dc.contributor.author","Pukrop, Tobias"],["dc.contributor.author","Koenig, Sarah"],["dc.date.accessioned","2018-11-07T10:13:22Z"],["dc.date.available","2018-11-07T10:13:22Z"],["dc.date.issued","2016"],["dc.description.abstract","Background: Wnt/beta-catenin signaling is known to play an important role in colorectal cancer (CRC). Niclosamide, a salicylamide derivative used in the treatment of tapeworm infections, targets the Wnt/beta-catenin pathway. The objective of this study was to investigate niclosamide as a therapeutic agent against CRC. Methods: The antiproliferative effects of 1, 3, 10, and 50 mu M concentrations of niclosamide on human (SW480 and SW620) and rodent (CC531) CRC cell lines were determined by MTS assay and direct cell count. The lymphoid enhancer-binding factor 1/transcription factor (LEF/TCF) reporter assay monitored the activity of Wnt signaling. Immunofluorescence staining demonstrated the expression pattern of active beta-catenin. Gene expression of canonical and noncanonical Wnt signaling components was analyzed using qRT-PCR. Western blot analysis was performed with antibodies detecting nuclear localization of beta-catenin and c-jun. Results: Cell proliferation in CRC cell lines was blocked dose dependently after 12 and 24 h of incubation. The Wnt promoter activity of LEF/TCF significantly decreased with niclosamide concentrations of 10 and 50 mM after 12 h of incubation. Active beta-catenin did not shift from the nuclear to the cytosolic pool. However, canonical target genes (met, MMP7, and cyclin D1) as well as the coactivating factor Bcl9 were downregulated, whereas the noncanonical key player c-jun was clearly activated. Conclusions: Niclosamide treatment is associated with an inhibitory effect on CRC development and reduced Wnt activity. It may exert its effect by interfering with the nuclear beta-catenin-Bcl9-LEF/TCF triple-complex and by upregulation of c-jun representing noncanonical Wnt/JNK signaling. Thus, our findings warrant further research into this substance as a treatment option for patients with advanced CRC. (C) 2016 Elsevier Inc. All rights reserved."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft [KO 2218/5-1]"],["dc.identifier.doi","10.1016/j.jss.2016.03.051"],["dc.identifier.isi","000378170200024"],["dc.identifier.pmid","27338550"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40422"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Academic Press Inc Elsevier Science"],["dc.relation.issn","1095-8673"],["dc.relation.issn","0022-4804"],["dc.title","The anthelmintic niclosamide inhibits colorectal cancer cell lines via modulation of the canonical and noncanonical Wnt signaling pathway"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]