ArticleThe Journal of biological chemistry2014
The intestinal epithelial cell differentiation marker intestinal alkaline phosphatase (ALPi) is selectively induced by histone deacetylase inhibitors (HDACi) in colon cancer cells in a Kruppel-like factor 5 (KLF5)-dependent manner.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 67 citations in OpenAlex.
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- Microbiota-derived metabolites in tumorigenesis: mechanistic insights and therapeutic implications.Frontiers in pharmacology · 2025Review
- IPA and its precursors differently modulate the proliferation, differentiation, and integrity of intestinal epithelial cells.Nutrition research and practice · 2023Article
- Intestinal Alkaline Phosphatase: A Review of This Enzyme Role in the Intestinal Barrier Function.Microorganisms · 2022Review
- Mechanism of Pterostilbene-Induced Cell Death in HT-29 Colon Cancer Cells.Molecules (Basel, Switzerland) · 2022Article
- Intestinal alkaline phosphatase deficiency increases the risk of diabetes.BMJ open diabetes research & care · 2022Article
- Role of Intestinal Alkaline Phosphatase in Innate Immunity.Biomolecules · 2021Review
- The roles and regulation of the KLF5 transcription factor in cancers.Cancer science · 2021Review
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- Small subset of Wnt-activated cells is an initiator of regrowth in colorectal cancer organoids after irradiation.Cancer science · 2020Article
- PRMT1 inhibition induces differentiation of colon cancer cells.Scientific reports · 2020Article
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- Histone Deacetylase Modifications by Probiotics in Colorectal Cancer.Journal of gastrointestinal cancer · 2020Review
- Tumor immune microenvironment and mutational analysis of tracheal adenoid cystic carcinoma.Annals of translational medicine · 2020Article
- High expression of Krüppel-like factor 5 is associated with poor prognosis in patients with colorectal cancer.Cancer science · 2020Article
Corrections and comments
- Erratum issuedThe intestinal epithelial cell differentiation marker intestinal alkaline phosphatase (ALPi) is selectively induced by histone deacetylase inhibitors (HDACi) in colon cancer cells in a Kruppel-like factor 5 (KLF5)-dependent manner.2015 · Dávaos-Salas, Mercedes [Corrected to Dávalos-Salas, Mercedes]
Authors and funding
21 authors at 10 institutions in 4 countries.
Funding
Abstract
The histone deacetylase inhibitor (HDACi) sodium butyrate promotes differentiation of colon cancer cells as evidenced by induced expression and enzyme activity of the differentiation marker intestinal alkaline phosphatase (ALPi). Screening of a panel of 33 colon cancer cell lines identified cell lines sensitive (42%) and resistant (58%) to butyrate induction of ALP activity. This differential sensitivity was similarly evident following treatment with the structurally distinct HDACi, MS-275. Resistant cell lines were significantly enriched for those harboring the CpG island methylator phenotype (p = 0.036, Chi square test), and resistant cell lines harbored methylation of the ALPi promoter, particularly of a CpG site within a critical KLF/Sp regulatory element required for butyrate induction of ALPi promoter activity. However, butyrate induction of an exogenous ALPi promoter-reporter paralleled up-regulation of endogenous ALPi expression across the cell lines, suggesting the presence or absence of a key transcriptional regulator is the major determinant of ALPi induction. Through microarray profiling of sensitive and resistant cell lines, we identified KLF5 to be both basally more highly expressed as well as preferentially induced by butyrate in sensitive cell lines. KLF5 overexpression induced ALPi promoter-reporter activity in resistant cell lines, KLF5 knockdown attenuated butyrate induction of ALPi expression in sensitive lines, and butyrate selectively enhanced KLF5 binding to the ALPi promoter in sensitive cells. These findings demonstrate that butyrate induction of the cell differentiation marker ALPi is mediated through KLF5 and identifies subsets of colon cancer cell lines responsive and refractory to this effect.
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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.