Investigating drivers of small cell lung cancer progression and metastasis
Abstract/Contents
- Abstract
- Most cancer patients die from the development of metastatic disease; however, the molecular mechanisms underlying metastatic progression remain poorly understood. Small cell lung cancer (SCLC) is a particularly metastatic disease in which tumor heterogeneity has hindered identification of many tumor drivers. Heterogeneity in SCLC is in part moderated by the Notch signaling pathway, and we found that modulating expression of the atypical Notch ligand DLL3 changes the balance of neuroendocrine and non-neuroendocrine cells within tumors. Furthermore, the transcription factor NFIB is a known driver of tumor growth and metastasis in SCLC, but the requirement for NFIB activity for tumor development has not been investigated in vivo. We developed conditional Nfib knockout mouse models of SCLC and found that NFIB contributes to tumor progression, but loss of NFIB does not prevent tumors from metastasizing using alternative mechanisms. We further identified the pioneer factor FOXA1 as a candidate NFIB-independent driver of SCLC. Our work shows the importance of identifying other drivers of SCLC progression and metastasis to fully understand the plasticity and heterogeneity of SCLC tumors.
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 | Ko, Julie Hyunjee |
|---|---|
| Degree supervisor | Sage, Julien |
| Thesis advisor | Sage, Julien |
| Thesis advisor | Pollack, Jonathan D |
| Thesis advisor | Winslow, Monte |
| Thesis advisor | van Rechem, Capucine |
| Degree committee member | Pollack, Jonathan D |
| Degree committee member | Winslow, Monte |
| Degree committee member | van Rechem, Capucine |
| Associated with | Stanford University, School of Medicine |
| Associated with | Stanford University, Cancer Biology Program |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Julie Ko. |
|---|---|
| Note | Submitted to the Cancer Biology Program. |
| Thesis | Thesis Ph.D. Stanford University 2023. |
| Location | https://purl.stanford.edu/xm548mp2026 |
Access conditions
- Copyright
- © 2023 by Julie Hyunjee Ko
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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