- Author
-
B.J. Meijer
- Title
- Maintenance and disruption of intestinal epithelial homeostasis
- Supervisors
-
G.R. van den Brink
- Co-supervisors
- Award date
- 10 September 2020
- Number of pages
- 189
- ISBN
- 9789493197152
- Document type
- PhD thesis
- Faculty
- Faculty of Medicine (AMC-UvA)
- Abstract
-
In this thesis the role of ER stress on the intestinal epithelial stem cell state in the context of colorectal cancer has been explored using different in vivo and in vitro genetically modified experimental models. Inactivation of APC is an early and key event in the development of colorectal cancer. This has attracted researchers to develop drugs that target molecules specific to APC-mutated cells. One of the main findings presented in this thesis is that ER stress reduces adenoma formation in the Apc-mutated mouse intestine. In addition, a deeper understanding of the underlying mechanism responsible for ER stress-induced loss of stemness is provided by identifying transcription factors altered upon ER stress. Furthermore, our ATF2 and ATF7 experiments demonstrate an uncoupling role of the ATF proteins in health and disease, a concept that provides key opportunities for the development of targeted therapies.
- Persistent Identifier
- https://hdl.handle.net/11245.1/6675109b-2236-44bd-9234-cd25ab7ed71b
- Downloads
-
Thesis (complete)
Front matter
Chapter 1: General introduction
Chapter 2: Induction of endoplasmic reticulum stress by deletion of Grp78 depletes Apc mutant intestinal epithelial stem cells
Chapter 3: Heterozygosity of UPR repressor Grp78 reduces intestinal stem cell regeneration potential and protects against adenoma formation
Chapter 4: Endoplasmic reticulum stress regulates the intestinal stem cell state through CtBP2
Chapter 5: Sirolimus for the treatment of severe intestinal polyposis in patients with familial adenomatous polyposis: A pilot study
Chapter 6 : ATF2 and ATF7 are critical mediators of intestinal epithelial repair
Chapter 7: Colorectal tumor prevention by the progestin Medroxyprogesterone Acetate is critically dependent on postmenopausal status
Chapter 8: Summary and future perspectives
Nederlandse samenvatting; List of contributing authors; Dankwoord
- Supplementary materials
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