Medicine and Health Sciences Commons^™

Strategies To Sensitize Bladder Cancer Cells To Small Molecule Inhibitors Targeting The Pi3k Pathway, Giovanni Nitti

Dissertations & Theses (Open Access)

After many years of cancer research, it is well accepted by the scientific community that the future cure for this disease lies in a personalized therapeutic approach. Anticipating therapeutic outcome based on the genetic signature of a tumor has become the new paradigm. The PI3K pathway represents an ideal target for bladder cancer, as many of the key proteins of this pathway are altered or mutated in this particular type of cancer. Several small molecule inhibitors have been developed to target this pathway, but their efficacy has been shown to be heterogeneous among different cell lines and mostly cytostatic but …

The Novel Upstream Regulator Of Fbxw7, Ji-Hyun Shin

Dissertations & Theses (Open Access)

SCF^FBXW7 is a tumor suppressor E3 ligase protein that targets numerous oncoproteins such as Cyclin E, c-Myc, c-Jun and MCL1. The deregulation of these proteins often leads to the proliferation of cancer cells. Thus, intracellular stability and functional activity of FBXW7 is critical for regulating cancer. However, there is a gap of knowledge about the intracellular signaling pathway or if there is another ubiquitin ligase that regulates FBXW7 stability. Here, I identify a novel mechanism of FBXW7 stability regulation which involves constitutive photomorphogenic 1 (COP1), AKT and CSN6 (i.e. the COP9 signalosome 6).

COP1 is an E3 ubiquitin ligase …