ArticleCell death & disease2022
Activation of FXR and inhibition of EZH2 synergistically inhibit colorectal cancer through cooperatively accelerating FXR nuclear location and upregulating CDX2 expression.
Article in Cell death & disease, 2022. 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 19 papers.
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Who cites it
19 citing papers in PubMed, 20 citations in OpenAlex.
- The JNK2-microbiome axis modulates gut barrier integrity through microbial acetate.Gut microbes · 2026Article
- Unveiling the New Trick for Epigenetic Drug: Radiation Enhancement of Prostate Cancer by the EZH2 Inhibitor Tazemetostat.Journal of cellular and molecular medicine · 2026Article
- Targeting the Epigenome in Colorectal Cancer.International journal of molecular sciences · 2026Review
- Epigenetic regulation and posttranslational modifications of FXR: underlying mechanisms and implications in digestive diseases.Acta pharmacologica Sinica · 2026Review
- Inhibition of circulating glycocholic acid-regulated signaling potentiates immune checkpoint therapy in colorectal cancer.Nature communications · 2026Article
- Prevention of cancer initiation by augmenting MHC-I antigen presentation via EZH2 inhibition.Oncogene · 2025Article
- DNA, RNA, and histone methylation regulation enzymes and their crosstalk in colorectal carcinogenesis and progression: a review of molecular mechanisms, clinical implications, and future perspectives.Cellular & molecular biology letters · 2025Review
- FXR activation suppresses NF-κB signaling, proliferation and migration in cervical cancer cells.Translational cancer research · 2025Article
- Crosstalk Between Bile Acids and Intestinal Epithelium: Multidimensional Roles of Farnesoid X Receptor and Takeda G Protein Receptor 5.International journal of molecular sciences · 2025Review
- Development and validation of nomograms for predicting overall survival and cancer-specific survival in unresected colorectal cancer patients undergoing chemotherapy.Scientific reports · 2025Article
- Article
- FXR promotes clear cell renal cell carcinoma carcinogenesis via MMP-7-regulated EMT pathway.Scientific reports · 2024Article
- Homeobox B9 promotes the invasion and metastasis of hepatocellular carcinoma cells via the EZH2-MIR203A-SNAI2 axis.Journal of translational medicine · 2024Article
- Hyodeoxycholic acid inhibits colorectal cancer proliferation through the FXR/EREG/EGFR axis.Frontiers in cell and developmental biology · 2024Article
- Review
- Anti-Glioma Effects of Ligustilide or n-Butylphthalide on Their Own and the Synergistic Effects with Temozolomide via PI3K/Akt Signaling Pathway.OncoTargets and therapy · 2023Article
- FXR agonist GW4064 enhances anti-PD-L1 immunotherapy in colorectal cancer.Oncoimmunology · 2023Article
- Promotion of Deoxycholic Acid Effect on Colonic Cancer Cell Lines In Vitro by Altering the Mucosal Microbiota.Microorganisms · 2022Article
- EZH2 as a Prognostic Factor and Its Immune Implication with Molecular Characterization in Prostate Cancer: An Integrated Multi-Omics in Silico Analysis.Biomolecules · 2022Article
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Our previous study indicated that colon cancer cells varied in sensitivity to pharmacological farnesoid X receptor (FXR) activation. Herein, we explore the regulatory mechanism of FXR in colorectal cancer (CRC) development and aim to design effective strategies of combined treatment based on the regulatory axis. We found that the expression of FXR was negatively correlated with enhancer of zeste homolog 2 (EZH2) in colon cancer tissues. EZH2 transcriptionally suppressed FXR via H3K27me3. The combination of FXR agonist OCA plus EZH2 inhibitor GSK126 acted in a synergistic manner across four colon cancer cells, efficiently inhibiting clonogenic growth and invasion in vitro, retarding tumor growth in vivo, preventing the G0/G1 to S phase transition, and inducing caspase-dependent apoptosis. Benign control cells FHC were growth-arrested without apoptosis induction, but retained long-term proliferation and invasion capacity. Mechanistically, the drug combination dramatically accelerated FXR nuclear location and cooperatively upregulated caudal-related homeobox transcription factor 2 (CDX2) expression. The depletion of CDX2 antagonized the synergistic effects of the drug combination on tumor inhibition. In conclusion, our study demonstrated histone modification-mediated FXR silencing by EZH2 in colorectal tumorigenesis, which offers useful evidence for the clinical use of FXR agonists combined with EZH2 inhibitors in combating CRC.
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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.