ArticleMolecular cancer research : MCR2008
Notch inhibits expression of the Krüppel-like factor 4 tumor suppressor in the intestinal epithelium.
Article in Molecular cancer research : MCR, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.
- Pooled it
- Porcine intestinal goblet cells: Guardians of mucosal immunity and barrier function.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2026Review
- VGLL4 modulates Paneth cells and sustains intestinal homeostasis.EMBO reports · 2026Article
- Review
- RIP140 regulates transcription factor HES1 oscillatory expression and mitogenic activity in colon cancer cells.Molecular oncology · 2024Article
- α-Ketoglutarate for Preventing and Managing Intestinal Epithelial Dysfunction.Advances in nutrition (Bethesda, Md.) · 2024Review
- Review
- Alpha-Ketoglutarate Promotes Goblet Cell Differentiation and Alters Urea Cycle Metabolites in DSS-Induced Colitis Mice.Nutrients · 2022Article
- Compromised Ileal Mucus Barrier Due to Impaired Epithelial Homeostasis Caused by Notch1 Signaling in Cirrhotic Rats.Digestive diseases and sciences · 2021Article
- Cell fate specification and differentiation in the adult mammalian intestine.Nature reviews. Molecular cell biology · 2021Review
- The Partial Role of KLF4 and KLF5 in Gastrointestinal Tumors.Gastroenterology research and practice · 2021Review
- Review
- KLF4 Regulates Goblet Cell Differentiation in BMI1International journal of stem cells · 2020Article
- Cancer Stem Cells,Cells · 2020Review
- Conjunctival goblet cells: Ocular surface functions, disorders that affect them, and the potential for their regeneration.The ocular surface · 2020Review
- Inflammation-induced colon cancer in uPA-deficient mice is associated with a deregulated expression of Notch signaling pathway components.Molecular and cellular biochemistry · 2020Article
- Notch3 signalling and vascular remodelling in pulmonary arterial hypertension.Clinical science (London, England : 1979) · 2019Review
- Concise Review: Regulation of Self-Renewal in Normal and Malignant Hematopoietic Stem Cells by Krüppel-Like Factor 4.Stem cells translational medicine · 2019Review
- Notch Represses Transcription by PRC2 Recruitment to the Ternary Complex.Molecular cancer research : MCR · 2017Article
- SP and KLF Transcription Factors in Digestive Physiology and Diseases.Gastroenterology · 2017Review
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The zinc finger-containing transcription factor, Krüppel-like factor 4 (KLF4), inhibits cell proliferation. An in vivo tumor-suppressive role for KLF4 is shown by the recent finding that Klf4 haploinsufficiency in Apc(Min/+) mice promotes intestinal tumorigenesis. Studies also show that KLF4 is required for the terminal differentiation of goblet cells in the mouse intestine. The Notch signaling pathway suppresses goblet cell formation and is up-regulated in intestinal tumors. Here, we investigated the relationship between Notch signaling and KLF4 expression in intestinal epithelial cells. The rate of proliferation of HT29 human colon cancer cells was reduced when treated with the gamma-secretase inhibitor dibenzazepine to inhibit Notch signaling or small interfering RNA directed against Notch. KLF4 levels were increased in dibenzazepine-treated or Notch small interfering RNA-treated cells. Conversely, overexpression of Notch in HT29 cells reduced KLF4 levels, suppressed KLF4 promoter activity, and increased proliferation rate. Treatment of Apc(Min/+) mice with dibenzazepine resulted in a 50% reduction in the number of intestinal adenomas compared with the vehicle-treated group (P < 0.001). Both the normal-appearing intestinal mucosa and adenomas obtained from dibenzazepine-treated Apc(Min/+) mice had increased goblet cell numbers and Klf4 staining accompanied by reduced cyclin D1 and Ki-67 staining when compared with those from vehicle-treated mice. Results of these studies indicate that Notch signaling suppresses KLF4 expression in intestinal tumors and colorectal cancer cells. Inhibition of Notch signaling increases KLF4 expression and goblet cell differentiation and reduces proliferation and tumor formation. KLF4 is therefore a potential mediator for the antitumor effect of Notch inhibitors such as dibenzazepine.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.