Cancer Biology Commons^™

Phos-Tag-Based Screens Identify Novel Therapeutic Targets In Ovarian Cancer And Pancreatic Cancer, Renya Zeng

Theses & Dissertations

Multiple Phos-tag-based screens were conducted in anti-tubulin drug (paclitaxel and nocodazole)-treated cells to explore novel targets implicated in cell cycle regulation, resistance against paclitaxel, and yes-associated protein (YAP) nucleocytoplasmic transport. The Phos-tag-based screen of protein kinases identified that several proteins were degraded or phosphorylated in response to anti-tubulin drug treatment. A tyrosine kinase, fibroblast growth factor receptor 4 (FGFR4), was significantly degraded upon anti-tubulin drug treatment, suggesting its potential role in cell response to paclitaxel. Further functional investigations identified that FGFR4 mediated paclitaxel resistance in ovarian cancer, and specific inhibitors targeting FGFR4 could sensitize ovarian cancer cells to paclitaxel. Mechanistically, …

Foxm1 Expression And Contribution To Genomic Instability And Chemoresistance In High-Grade Serous Ovarian Cancer, Carter J. Barger

Theses & Dissertations

High-grade serous ovarian cancer (HGSC) is the most common and deadly subtype of epithelial ovarian cancer. Understanding the molecular basis of HGSC will improve diagnosis and treatment approaches. The Cancer Genome Atlas (TCGA) discovered that Forkhead Box M1 (FOXM1) transcription factor activation is the second most frequent molecular alteration in HGSC (84% of cases), second only to mutations of TP53 (100%). We subsequently defined several genetic mechanisms that underlie increased FOXM1 expression in HGSC, including genomic amplifications and RB-E2F deregulation, and showed that FOXM1 promotes cell cycle progression in cell models relevant to HGSC.

TCGA analyses revealed that genomic instability, …

The Role Of Yes-Associated Protein 1 In Ovarian Physiology And Pathology, Xiangmin Lv

Theses & Dissertations

Ovarian granulosa cells are the major somatic components of the ovarian follicle. Proper proliferation and differentiation of ovarian granulosa cells are essential for successful follicle development. Accumulating evidence indicates that the Hippo-YAP signaling pathway plays critical roles in both development and tumorigenesis of several organs. The present study aims to investigate the role of Yes-associated protein 1 (YAP) in ovarian granulosa cell proliferation, differentiation, and malignant transformation. At first, we found that nuclear YAP (active) was highly expressed in proliferative granulosa cells, whereas cytoplasmic YAP (inactive) was detected mainly in terminally-differentiated luteal cells. Further studies suggested that endogenous YAP activity …