Tumor establishment requires tumor autonomous and non-autonomous decoupling of EGF signaling from apoptosis
Abstract/Contents
- Abstract
- In homeostasis, robust mechanisms enforce a balanced equilibrium between cell division and death. Nascent tumors must destabilize tissue-level homeostatic controls to subvert cell equilibrium for cancerous growth. Though central to understanding how new tumors become established, the mechanisms underlying these destabilizing events are poorly understood. One of the best characterized mechanisms for cell equilibrium is that of the adult Drosophila intestine. In this organ, division is coupled to death because Rhomboid, a protease that cleaves mitogenic epidermal growth factors (EGFs) for secretion, is induced in cells undergoing apoptotic elimination6. In Drosophila, as in mammals, intestinal stem cells give rise to adenomas following loss of adenomatous polyposis coli (APC). Examining Drosophila APC-/- tumorigenesis, we find that pre-tumor cells destabilize cell equilibrium by uncoupling rhomboid from apoptosis, which creates feed-forward amplification of EGF signaling for tumor establishment. Prior to tumor formation, APC-/- cells induce rhomboid in surrounding cells via activation of the stress signal JNK. During subsequent growth, APC-/- tumors induce rhomboid within the tumor itself via loss of E-cadherin and consequent activity of p120-catenin. Chronic induction of rhomboid in both tumor and surrounding cells leads to constitutive activation of EGFR and is essential for tumors to progress. Thus, incipient tumors combine non-autonomous and autonomous strategies to deregulate rhomboid and destabilize cell equilibrium. Since Rhomboid, EGFR, and E cadherin are associated with colorectal cancer in humans, our findings may shed light on how human colorectal tumors progress.
Description
| Type of resource | text |
|---|---|
| Date created | June 2019 |
Creators/Contributors
| Author | Ngo, Sang | |
|---|---|---|
| Primary advisor | O'Brien, Lucy | |
| Advisor | Luo, Liqun | |
| Degree granting institution | Stanford University, Department of Biology 2019 |
Subjects
| Subject | Biology |
|---|---|
| Subject | Molecular and Cellular Physiology |
| Genre | Thesis |
Bibliographic information
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- User agrees that, where applicable, content will not be used to identify or to otherwise infringe the privacy or confidentiality rights of individuals. Content distributed via the Stanford Digital Repository may be subject to additional license and use restrictions applied by the depositor.
- License
- This work is licensed under a Creative Commons Attribution Share Alike 3.0 Unported license (CC BY-SA).
Preferred citation
- Preferred Citation
- Ngo, Sang, O'Brien, Lucy & Luo, Liqun. (2019). Tumor establishment requires tumor autonomous and non-autonomous decoupling of EGF signaling from apoptosis. Stanford Digital Repository. Available at: https://purl.stanford.edu/jv911yr1661
Collection
Undergraduate Theses, Department of Biology, 2018-2019
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- sqn11525@stanford.edu
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