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Regulatory And Functional Aspects Of Foxo3a Transcription Factor And Their Implications In Prostate Cancer, Melissa Elise Dobson
Regulatory And Functional Aspects Of Foxo3a Transcription Factor And Their Implications In Prostate Cancer, Melissa Elise Dobson
Wayne State University Dissertations
The P13K/Akt pathway is a critical mediator of growth factor signaling involving many cellular functions. The deregulation of this pathway has been shown to be involved in the development of various cancers. One of the main targets of this pathway is FoxO3a, a transcription factor whose target genes are involved in important cellular processes such as apoptosis, cell cycle control, and glucose metabolism. FoxO3a is regulated by various post translational modifications including acetylation, ubiquitination and phosphorylation. The transcription factor is directly phosphorylated by Akt on 3 residues: Threonine 32, Serine 253 and Serine 315. Phosphorylation by Akt generates binding sites …
Matriptase/Pdgf D/Beta-Pdgfr Signaling Axis In Human Prostate Cancer: The Role Of Pten In The Regulation Of Pdgf D Expression, M. Katie Conley-Lacomb
Matriptase/Pdgf D/Beta-Pdgfr Signaling Axis In Human Prostate Cancer: The Role Of Pten In The Regulation Of Pdgf D Expression, M. Katie Conley-Lacomb
Wayne State University Dissertations
Platelet Derived Growth Factor (PDGF) is a family of mesenchymal growth factors that regulate cell proliferation, migration, and differentiation. Unlike the classic PDGF ligands A and B, which are secreted as active dimers, PDGF D must undergo extracellular proteolytic processing to remove its N-terminal CUB domain from the C-terminal PDGF growth domain before the ligand is able to stimulate its receptor, PDGF receptor beta (?-PDGFR). Importantly, recent clinical studies have shown that ?-PDGFR is upregulated in primary prostate cancer and bone metastases. However, PDGF B, formerly thought to be the sole ligand for ?-PDGFR, is not expressed in clinical prostate …
Induction And Regulation Of Autophagy By Novel Prenylation Inhibitors In Sts-26t Malignant Peripheral Nerve Sheath Tumor (Mpnst) Cells, Komal Madhukar Sane
Induction And Regulation Of Autophagy By Novel Prenylation Inhibitors In Sts-26t Malignant Peripheral Nerve Sheath Tumor (Mpnst) Cells, Komal Madhukar Sane
Wayne State University Dissertations
Prenylation pathways have been targeted via several different compounds that inhibit farnesyl transferase (FTase) and/or geranylgeranyl transferase (GGTase) enzymes in many cellular and animal models of cancer. Some of these have also been evaluated in clinical trials with limited success. Multiple mechanisms of action have been elucidated for such compounds, including cell cycle arrest, proteasome inhibition, apoptosis and most recently, autophagy. However, there is still an urgent need of effective agents of this class of anti-tumor therapeutics. In this dissertation, I sought to delve into this issue by characterizing our novel prenylation inhibitors and their potential as anti-tumor agents. Novel …