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TWEAK functions as chemotactic factor for glioma cells via Lyn activation

Description
The long-term survival of patients with glioblastoma multiforme is compromised by the tumor's proclivity for local invasion into the surrounding normal brain. These invasive cells escape surgery and display resistance to chemotherapeutic- and radiation-induced apoptosis. We have previously shown that tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member…

The long-term survival of patients with glioblastoma multiforme is compromised by the tumor's proclivity for local invasion into the surrounding normal brain. These invasive cells escape surgery and display resistance to chemotherapeutic- and radiation-induced apoptosis. We have previously shown that tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor superfamily, can stimulate glioma cell invasion and survival via binding to the fibroblast growth factor-inducible 14 (Fn14) receptor and subsequent activation of the Rac1/NF-kappaB pathway. In addition, we have reported previously that Fn14 is expressed at high levels in migrating glioma cells in vitro and invading glioma cells in vivo. Here we demonstrate that TWEAK can act as a chemotactic factor for glioma cells, a potential process to drive cell invasion into the surrounding brain tissue. Specifically, we detected a chemotactic migration of glioma cells to the concentration gradient of TWEAK. Since Src family kinases (SFK) have been implicated in chemotaxis, we next determined whether TWEAK:Fn14 engagement activated these cytoplasmic tyrosine kinases. Our data shows that TWEAK stimulation of glioma cells results in a rapid phosphorylation of the SFK member Lyn as determined by multiplex Luminex assay and verified by immunoprecipitation. Immunodepletion of Lyn by siRNA oligonucleotides suppressed the chemoattractive effect of TWEAK on glioma cells. We hypothesize that TWEAK secretion by cells present in the glioma microenvironment induce invasion of glioma cells into the brain parenchyma. Understanding the function and signaling of the TWEAK-Fn14 ligand-receptor system may lead to development of novel therapies to therapeutically target invasive glioma cells.
ContributorsJameson, Nathan Meade (Author) / Anderson, Karen (Thesis director) / Lake, Douglas (Committee member) / Tran, Nhan (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2013-05
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A List-based App Launcher Tweak for Jailbroken iOS Devices

Description
Finding applications on Apple’s iOS device Home screen is a difficult task since applications are arranged in a disorganized grid of icons and small labels. By “jailbreaking” an iOS device, it is possible to install third party “tweaks” that modify the operating system to customize and fix annoying aspects of…

Finding applications on Apple’s iOS device Home screen is a difficult task since applications are arranged in a disorganized grid of icons and small labels. By “jailbreaking” an iOS device, it is possible to install third party “tweaks” that modify the operating system to customize and fix annoying aspects of iOS. Current jailbreak tweaks exist that can launch applications differently than Apple’s stock Home screen, but they leave much to be desired in terms of functionality, usability, and aesthetics. HomeList is a watchOS-inspired tweak I created to add an easy to read, quick to navigate, and visually appealing list of applications integrated directly into the Home screen. Research into Apple’s private iOS frameworks was used to figure out how to perform tasks required by an app launcher as well as match iOS design aesthetics.
ContributorsBoxberger, Blake Palmer (Author) / Balasooriya, Janaka (Thesis director) / Faucon, Philippe Christophe (Committee member) / Computer Science and Engineering Program (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05