Researcher ORCID Identifier
Campus Only Senior Thesis
Bachelor of Arts
© 2022 Tiffany TK Pham
Ovarian cancer is a lethal gynecological cancer; one subtype, high-grade serous ovarian cancer (HGSOC), remains the most common and aggressive. Two genes encoding transcription factors are focally amplified in HGSOC: Heat Shock Factor 1 (HSF1) and c- Myc. HSF1 is a regulator of the heat shock response (HSR) to the disruption of proteostasis. In turn, c-Myc is a regulator of the expression of about 15% of human the human genome —directing a wide array of pathways including cell cycle progression, metabolism, and differentiation—and correlates directly with HGSOC grade at both the transcript and protein levels. Previous studies have suggested that in HGSOC, HSF1 promotes the ability of cells to grow under conditions of low cell density, promotes cell motility and invasiveness, and is implicated in the epithelial-to-mesenchymal transition (EMT). To further characterize how HSF1 and c-Myc interact to drive HGSOC, we performed qRT-PCR, colony formation assays, and scratch assays. From these efforts, we first determined that c-Myc siRNA-mediated knockdown led to a significant decrease in the expression of an HSF1 target, hHSP70 (p < 0.05). Second, we determined that double-knockdown of c-Myc and HSF1 led to a significant increase in the expression of c-Myc-target, E-cadherin—a transmembrane protein that adheres neighboring cells—decreasing the metastatic potential of HGSOC cells. Third, we determined that colony proliferation capacity was almost entirely eradicated by low concentrations of siRNA, further validating the role of HSF1 and c-Myc in HGSOC. Taken together, this study motivates future work into the coordination between HSF1 and c-Myc in HGSOC, with the potential to identify mechanisms that hold promising therapeutic vulnerability.
Pham, Tiffany, "Partners in Crime? HSF1 and c-Myc in High-Grade Serous Ovarian Cancer" (2023). Scripps Senior Theses. 2005.
Available for download on Tuesday, December 12, 2023
This thesis is restricted to the Claremont Colleges current faculty, students, and staff.