{"@context":"http://iiif.io/api/presentation/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/manifest.json","@type":"sc:Manifest","label":"Dual Role of Chibby in Regulation of Cell Growth and Mesenchymal-to-Epithelial Transition-like Processes","metadata":[{"label":"dc.description.sponsorship","value":"This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree."},{"label":"dc.format","value":"Monograph"},{"label":"dc.format.medium","value":"Electronic Resource"},{"label":"dc.identifier.uri","value":"http://hdl.handle.net/1951/59646"},{"label":"dc.language.iso","value":"en_US"},{"label":"dc.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.abstract","value":"The Wnt/beta-catenin signaling pathway is well known for its prominent role in tumorigenesis of colon cancers, but also of some other tumors. Beta-Catenin, the downstream mediator of canonical Wnt-signaling, is continuously degraded in the absence of Wnt signaling but stabilized upon activation of the pathway. Beta-Catenin then activates transcription of target genes in the nucleus, leading e.g. to proliferation, invasiveness and anoikis resistance, and can induce epithelial-to-mesenchymal transition (EMT). Apart from its function as a transcriptional coactivator, beta-catenin forms part of adherens junctions where it plays a pivotal role mediating the connection between the adherens junction protein E-cadherin and the actin cytoskeleton, and its loss from the membrane entrails reduced cell-cell adhesion. This role contrasts beta-catenin's function in the nucleus since formation of E-cadherin-mediated adherens junctions reverses a malignant phenotype, effectuating mesenchymal-to-epithelial transition (MET), in a variety of tumor cell lines. The small, evolutionarily conserved protein Chibby was initially discovered as beta-catenin binding partner. Our lab has shown that Chibby shuttles beta-catenin out of the nucleus, in cooperation with 14-3-3 proteins. By this mechanism and by competing with T-cell factor/lymphoid enhancer factor (TCF/LEF) transcription factors for beta-catenin binding, Chibby inhibits nuclear beta-catenin signaling. We show here that Chibby counteracts both of beta-catenin's opposing roles in that a) Chibby can reduce beta-catenin nuclear signaling and cell proliferation in human colon cancer cells bearing stabilized beta-catenin by reducing nuclear levels of beta-catenin, and that b) Chibby knock-down leads to increased proteins levels of E-cadherin and beta-catenin at the plasma membrane, to the point of inducing mesenchymal-to-epithelial reversion with reduced tumor characteristics in human embryonic kidney and human colon cancer cells, and that this is due at least in part to increased transcription of the E-cadherin gene. These findings are relevant to further development of treatment options for Wnt/beta-catenin-dependent tumors."},{"label":"dcterms.available","value":"2015-04-24T14:46:33Z"},{"label":"dcterms.contributor","value":"Brown, Deborah A."},{"label":"dcterms.creator","value":"Fischer, Victoria"},{"label":"dcterms.dateAccepted","value":"2013-05-22T17:34:31Z"},{"label":"dcterms.dateSubmitted","value":"2015-04-24T14:46:33Z"},{"label":"dcterms.description","value":"Department of Molecular and Cellular Pharmacology"},{"label":"dcterms.extent","value":"79 pg."},{"label":"dcterms.format","value":"Application/PDF"},{"label":"dcterms.identifier","value":"http://hdl.handle.net/11401/71219"},{"label":"dcterms.issued","value":"2012-05-01"},{"label":"dcterms.language","value":"en_US"},{"label":"dcterms.provenance","value":"Made available in DSpace on 2015-04-24T14:46:33Z (GMT). No. of bitstreams: 3\nFischer_grad.sunysb_0771E_10991.pdf.jpg: 1894 bytes, checksum: a6009c46e6ec8251b348085684cba80d (MD5)\nFischer_grad.sunysb_0771E_10991.pdf.txt: 172683 bytes, checksum: cb9fdf43afb54e896eb01f44204fd873 (MD5)\nFischer_grad.sunysb_0771E_10991.pdf: 2335468 bytes, checksum: 68f1d9fb3a1aa61c89acd9e1de1e8ef1 (MD5)\n  Previous issue date:    1"},{"label":"dcterms.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.subject","value":"beta-catenin, Chibby, colon cancer, epithelial-to-mesenchymal transition, Wnt-signaling"},{"label":"dcterms.title","value":"Dual Role of Chibby in Regulation of Cell Growth and Mesenchymal-to-Epithelial Transition-like Processes"},{"label":"dcterms.type","value":"Dissertation"},{"label":"dc.type","value":"Dissertation"}],"description":"This manifest was generated dynamically","viewingDirection":"left-to-right","sequences":[{"@type":"sc:Sequence","canvases":[{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json","@type":"sc:Canvas","label":"Page 1","height":1650,"width":1275,"images":[{"@type":"oa:Annotation","motivation":"sc:painting","resource":{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/14%2F50%2F00%2F145000359562478422487327352670854912055/full/full/0/default.jpg","@type":"dctypes:Image","format":"image/jpeg","height":1650,"width":1275,"service":{"@context":"http://iiif.io/api/image/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/14%2F50%2F00%2F145000359562478422487327352670854912055","profile":"http://iiif.io/api/image/2/level2.json"}},"on":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json"}]}]}]}