| dc.identifier.uri | http://hdl.handle.net/11401/77637 | |
| dc.description.sponsorship | This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. | en_US |
| dc.format | Monograph | |
| dc.format.medium | Electronic Resource | en_US |
| dc.language.iso | en_US | |
| dc.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dc.type | Dissertation | |
| dcterms.abstract | 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. | |
| dcterms.available | 2017-09-20T16:53:07Z | |
| dcterms.contributor | Van Aelst, Linda | en_US |
| dcterms.contributor | Tuveson, David | en_US |
| dcterms.contributor | Thomsen, Gerald | en_US |
| dcterms.contributor | Egeblad, Mikala | en_US |
| dcterms.contributor | Philips, Mark. | en_US |
| dcterms.creator | Yu, Jia-Ray | |
| dcterms.dateAccepted | 2017-09-20T16:53:07Z | |
| dcterms.dateSubmitted | 2017-09-20T16:53:07Z | |
| dcterms.description | Department of Genetics. | en_US |
| dcterms.extent | 94 pg. | en_US |
| dcterms.format | Monograph | |
| dcterms.format | Application/PDF | en_US |
| dcterms.identifier | http://hdl.handle.net/11401/77637 | |
| dcterms.issued | 2015-12-01 | |
| dcterms.language | en_US | |
| dcterms.provenance | Made available in DSpace on 2017-09-20T16:53:07Z (GMT). No. of bitstreams: 1
Yu_grad.sunysb_0771E_12244.pdf: 5741851 bytes, checksum: aa67f951c9734b884d4f54323e5505c8 (MD5)
Previous issue date: 1 | en |
| dcterms.publisher | The Graduate School, Stony Brook University: Stony Brook, NY. | |
| dcterms.subject | DOCK180, Extravasation, Metastasis, Rac1, TGF-beta | |
| dcterms.subject | Genetics | |
| dcterms.title | TGF-β /Smad signaling through DOCK4 facilitates lung adenocarcinoma metastasis | |
| dcterms.type | Dissertation | |
