Type
Text
Type
Dissertation
Advisor
Van Aelst, Linda | Tuveson, David | Thomsen, Gerald | Egeblad, Mikala | Philips, Mark.
Date
2015-12-01
Keywords
DOCK180, Extravasation, Metastasis, Rac1, TGF-beta | Genetics
Department
Department of Genetics.
Language
en_US
Source
This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree.
Identifier
http://hdl.handle.net/11401/77637
Publisher
The Graduate School, Stony Brook University: Stony Brook, NY.
Format
application/pdf
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. | 94 pages
Recommended Citation
Yu, Jia-Ray, "TGF-β /Smad signaling through DOCK4 facilitates lung adenocarcinoma metastasis" (2015). Stony Brook Theses and Dissertations Collection, 2006-2020 (closed to submissions). 3432.
https://commons.library.stonybrook.edu/stony-brook-theses-and-dissertations-collection/3432