{"@context":"http://iiif.io/api/presentation/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/manifest.json","@type":"sc:Manifest","label":"TGF-β /Smad signaling through DOCK4 facilitates lung adenocarcinoma metastasis","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/11401/77637"},{"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 mechanisms by which transforming growth factor beta (TGF-beta) promotes lung adenocarcinoma (ADC) metastasis are largely unknown. Here, we report that in lung ADC cells TGF-beta potently induces expression of dedicator of cytokinesis 4 (DOCK4), but not other DOCK-family members, via the Smad pathway, and that DOCK4 induction mediates TGF-beta's pro-metastatic effects by enhancing tumor cell extravasation. TGF-beta-induced DOCK4 stimulates lung ADC cell protrusion, motility, and invasion, without affecting epithelial-to-mesenchymal transition (EMT). These processes, which are fundamental to tumor cell extravasation, are driven by DOCK4-mediated Rac1 activation, unveiling a novel link between TGF-beta and Rac1. Thus, our findings uncover the atypical Rac1 activator DOCK4 as a key component of the TGF-beta/Smad pathway that promotes lung ADC cell extravasation and metastasis."},{"label":"dcterms.available","value":"2017-09-20T16:53:07Z"},{"label":"dcterms.contributor","value":"Thomsen, Gerald"},{"label":"dcterms.creator","value":"Yu, Jia-Ray"},{"label":"dcterms.dateAccepted","value":"2017-09-20T16:53:07Z"},{"label":"dcterms.dateSubmitted","value":"2017-09-20T16:53:07Z"},{"label":"dcterms.description","value":"Department of Genetics."},{"label":"dcterms.extent","value":"94 pg."},{"label":"dcterms.format","value":"Application/PDF"},{"label":"dcterms.identifier","value":"http://hdl.handle.net/11401/77637"},{"label":"dcterms.issued","value":"2015-12-01"},{"label":"dcterms.language","value":"en_US"},{"label":"dcterms.provenance","value":"Made available in DSpace on 2017-09-20T16:53:07Z (GMT). No. of bitstreams: 1\nYu_grad.sunysb_0771E_12244.pdf: 5741851 bytes, checksum: aa67f951c9734b884d4f54323e5505c8 (MD5)\n  Previous issue date:    1"},{"label":"dcterms.publisher","value":"The Graduate School, Stony Brook University: Stony Brook, NY."},{"label":"dcterms.subject","value":"Genetics"},{"label":"dcterms.title","value":"TGF-β /Smad signaling through DOCK4 facilitates lung adenocarcinoma metastasis"},{"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/2/81%2F07%2F48%2F81074868512841995139990380441234082025/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/2/81%2F07%2F48%2F81074868512841995139990380441234082025","profile":"http://iiif.io/api/image/2/level2.json"}},"on":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json"}]}]}]}