The stairway to heaven : EMP2 links cell cycle arrest, lipid metabolism, and ferroptosis sensitivity
Abstract/Contents
- Abstract
- Ferroptosis is a non-apoptotic form of cell death that can be triggered by inhibiting the system xc- cystine/glutamate antiporter or the phospholipid hydroperoxidase glutathione peroxidase 4 (GPX4). Here, we show that cells arrested in the cell cycle by stabilization of wild type p53 or by inhibition of cyclin-dependent kinase activity have increased sensitivity to GPX4 inhibitors but not system xc- inhibitors. Cell cycle arrest alters the lipidome to increase the abundance of oxidizable polyunsaturated fatty acid-containing phospholipids (PUFA-PLs), which drives sensitivity to GPX4 inhibitors. Changes in PUFA-PL abundance upon cell cycle arrest are linked to reduced expression of membrane bound O-acyltransferase domain containing 1 (MBOAT1) and epithelial membrane protein 2 (EMP2). A candidate orally bioavailable GPX4 inhibitor increased ferroptotic lipid peroxidation and shrunk tumor volumes when combined with a CDK4/6 inhibitor. Thus, cell cycle arrest may make certain cancer cells more susceptible to ferroptosis in vivo.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2023; ©2023 |
| Publication date | 2023; 2023 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Rodencal, Jason Jeffrey |
|---|---|
| Degree supervisor | Dixon, Scott James, 1977- |
| Thesis advisor | Dixon, Scott James, 1977- |
| Thesis advisor | Long, Jonathan Z |
| Thesis advisor | Sage, Julien |
| Thesis advisor | Skotheim, Jan, 1977- |
| Degree committee member | Long, Jonathan Z |
| Degree committee member | Sage, Julien |
| Degree committee member | Skotheim, Jan, 1977- |
| Associated with | Stanford University, School of Medicine |
| Associated with | Stanford University, Cancer Biology Program |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Jason Jeffrey Rodencal. |
|---|---|
| Note | Submitted to the Cancer Biology Program. |
| Thesis | Thesis Ph.D. Stanford University 2023. |
| Location | https://purl.stanford.edu/jc611wm5528 |
Access conditions
- Copyright
- © 2023 by Jason Jeffrey Rodencal
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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