Molecular origins of heterogeneity in cancer cell death
Abstract/Contents
- Abstract
- Anti-cancer drugs and other lethal agents can induce heterogeneous cell death responses in a population of cancer cells, a phenomenon referred to as fractional killing (FK). FK arises from a wide variety of molecular mechanisms, the study of which has been limited by inadequate tools for quantifying and studying cell death. We have developed and validated methods to quantify FK in a high-throughput manner. Here, I use this approach to investigate FK induced by inhibitors of mitogen activated protein kinase kinase (MEK) 1/2. I show that Bcl-2 family members play a critical role in executing cell death upon MEK inhibition, and that among pro-survival Bcl-2 family members, MCL1 (and not BCL-xL) is an important determinant of FK. I show that JNK activity modulates MEK inhibitor-induced death via effects on MCL1. These effects are consistent across some, but not all cell lines, suggesting that generalizable molecular models of FK are rare. These studies lay the foundation for quantitative high-throughput analyses of FK
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 | 2020; ©2020 |
| Publication date | 2020; 2020 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Inde, Zintis Raimonds |
|---|---|
| Degree supervisor | Dixon, Scott James, 1977- |
| Thesis advisor | Dixon, Scott James, 1977- |
| Thesis advisor | Bassik, Michael |
| Thesis advisor | Morrison, Ashby J |
| Degree committee member | Bassik, Michael |
| Degree committee member | Morrison, Ashby J |
| Associated with | Stanford University, Cancer Biology Program. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Zintis R. Inde |
|---|---|
| Note | Submitted to the Cancer Biology Program |
| Thesis | Thesis Ph.D. Stanford University 2020 |
| Location | electronic resource |
Access conditions
- Copyright
- © 2020 by Zintis Raimonds Inde
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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