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Krüppel-like factor 4 regulates intestinal epithelial cell morphology and polarity
- Source :
- PLoS ONE, Vol 7, Iss 2, p e32492 (2012), PLoS ONE
- Publication Year :
- 2012
- Publisher :
- Public Library of Science (PLoS), 2012.
-
Abstract
- Krüppel-like factor 4 (KLF4) is a zinc finger transcription factor that plays a vital role in regulating cell lineage differentiation during development and maintaining epithelial homeostasis in the intestine. In normal intestine, KLF4 is predominantly expressed in the differentiated epithelial cells. It has been identified as a tumor suppressor in colorectal cancer. KLF4 knockout mice demonstrated a decrease in number of goblet cells in the colon, and conditional ablation of KLF4 from the intestinal epithelium led to altered epithelial homeostasis. However, the role of KLF4 in differentiated intestinal cells and colon cancer cells, as well as the mechanism by which it regulates homeostasis and represses tumorigenesis in the intestine is not well understood. In our study, KLF4 was partially depleted in the differentiated intestinal epithelial cells by a tamoxifen-inducible Cre recombinase. We found a significant increase in the number of goblet cells in the KLF4-deleted small intestine, suggesting that KLF4 is not only required for goblet cell differentiation, but also required for maintaining goblet cell numbers through its function in inhibiting cell proliferation. The number and position of Paneth cells also changed. This is consistent with the KLF4 knockout study using villin-Cre [1]. Through immunohistochemistry (IHC) staining and statistical analysis, we found that a stem cell and/or tuft cell marker, DCAMKL1, and a proliferation marker, Ki67, are affected by KLF4 depletion, while an enteroendocrine cell marker, neurotensin (NT), was not affected. In addition, we found KLF4 depletion altered the morphology and polarity of the intestinal epithelial cells. Using a three-dimensional (3D) intestinal epithelial cyst formation assay, we found that KLF4 is essential for cell polarity and crypt-cyst formation in human colon cancer cells. These findings suggest that, as a tumor suppressor in colorectal cancer, KLF4 affects intestinal epithelial cell morphology by regulating proliferation, differentiation and polarity of the cells.
- Subjects :
- Chromosomes, Artificial, Bacterial
Pathology
Cellular differentiation
Gene Expression
lcsh:Medicine
Enteroendocrine cell
Mice
0302 clinical medicine
Molecular Cell Biology
Cell polarity
Signaling in Cellular Processes
Homeostasis
lcsh:Science
Mice, Knockout
0303 health sciences
Multidisciplinary
Mechanisms of Signal Transduction
Animal Models
Signaling in Selected Disciplines
Immunohistochemistry
Intestinal epithelium
3. Good health
Cell biology
Gene Expression Regulation, Neoplastic
Intestines
medicine.anatomical_structure
KLF4
030220 oncology & carcinogenesis
Colonic Neoplasms
embryonic structures
Medicine
Cellular Types
Stem cell
Tuft cell
biological phenomena, cell phenomena, and immunity
Research Article
Signal Transduction
medicine.medical_specialty
DNA, Complementary
Immunology
Kruppel-Like Transcription Factors
Mice, Transgenic
Biology
Kruppel-Like Factor 4
03 medical and health sciences
Model Organisms
stomatognathic system
Intestinal Neoplasms
medicine
Animals
Humans
030304 developmental biology
Goblet cell
fungi
lcsh:R
Epithelial Cells
Immunologic Techniques
Clinical Immunology
lcsh:Q
sense organs
Caco-2 Cells
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 7
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....c46b34d1f8fe7ebef33fd4568dbdafd9