Fang, Richard
(2024)
Exploiting ferroptosis as a therapeutic vulnerability in cyclin E1-high ovarian cancers.
Undergraduate Thesis, University of Pittsburgh.
(Unpublished)
Abstract
Among ovarian cancer subtypes, CCNE1-amplification is frequently associated with aggressive tumor growth and limited treatment options, resulting from homologous recombination (HR) proficiency and a subsequent de novo resistance to DNA damaging agents. This underscores a need for alternative, targeted therapies. Ferroptosis is an iron-dependent form of regulated cell death, characterized by generation of reactive oxygen species (ROS) and excessive membrane peroxidation leading to cellular death. Here, we present the metabolic consequences of cyclin E1 overexpression highlighting ferroptosis as a vulnerability of this ovarian cancer profile. We demonstrate that cyclin E1 overexpression promotes a proliferative phenotype that correlates with an upregulation of iron-containing proteins that are involved in DNA replication and repair. We also demonstrate that cyclin E1-high cells exhibit a marked increase in labile iron content, potentially to meet an increased iron demand, which in turn leads to elevated ROS production. This increase in labile iron and ROS sensitizes cyclin E1-high cells to ferroptosis, while treatment with ferroptosis inhibitors and antioxidants rescues cell viability. Our findings highlight the link between cyclin E-overexpression and dysregulated iron metabolism in ovarian cancer, offering a novel therapeutic opportunity. By targeting ferroptosis in cyclin E1-amplified tumors, these results suggest a novel strategy to treat this aggressive cancer subtype.
Share
| Citation/Export: |
|
| Social Networking: |
|
Details
| Item Type: |
University of Pittsburgh ETD
|
| Status: |
Unpublished |
| Creators/Authors: |
|
| ETD Committee: |
|
| Date: |
16 December 2024 |
| Date Type: |
Publication |
| Defense Date: |
6 November 2024 |
| Approval Date: |
16 December 2024 |
| Submission Date: |
9 December 2024 |
| Access Restriction: |
2 year -- Restrict access to University of Pittsburgh for a period of 2 years. |
| Number of Pages: |
83 |
| Institution: |
University of Pittsburgh |
| Schools and Programs: |
David C. Frederick Honors College |
| Degree: |
BPhil - Bachelor of Philosophy |
| Thesis Type: |
Undergraduate Thesis |
| Refereed: |
Yes |
| Uncontrolled Keywords: |
ferroptosis, cyclin E1, ovarian cancer, iron metabolism |
| Date Deposited: |
16 Dec 2024 13:54 |
| Last Modified: |
16 Dec 2024 13:54 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/47212 |
Metrics
Monthly Views for the past 3 years
Plum Analytics
Actions (login required)
 |
View Item |
![[img]](https://d-scholarship.pitt.edu/style/images/fileicons/application_pdf.png)
![[feed]](/images/feed-icon-32x32.png){kind=icon}