ArticleNeoplasia (New York, N.Y.)2019
Epigenetically Down-Regulated Acetyltransferase PCAF Increases the Resistance of Colorectal Cancer to 5-Fluorouracil.
Article in Neoplasia (New York, N.Y.), 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 41 citations in OpenAlex.
- Loss of PCAF in proximal tubular cells exacerbates renal fibrosis by promoting partial epithelial-to-mesenchymal transition.Experimental & molecular medicine · 2025Article
- Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer.International journal of molecular sciences · 2025Review
- The role of acetylation and deacetylation in cancer metabolism.Clinical and translational medicine · 2025Review
- Functional Investigations of p53 Acetylation Enabled by Heterobifunctional Molecules.ACS chemical biology · 2024Article
- PCAF promotes R-loop resolution via histone acetylation.Nucleic acids research · 2024Article
- The histone lysine acetyltransferase KAT2B inhibits cholangiocarcinoma growth: evidence for interaction with SP1 to regulate NF2-YAP signaling.Journal of experimental & clinical cancer research : CR · 2024Article
- PCAF acetylates AIB1 to form a transcriptional coactivator complex to promote glycolysis in endometrial cancer.Frontiers in oncology · 2024Article
- Unlocking the potential of targeting histone-modifying enzymes for treating IBD and CRC.Clinical epigenetics · 2023Review
- TIMP-2 as a predictive biomarker in 5-Fu-resistant colorectal cancer.Journal of cancer research and clinical oncology · 2023Article
- Downregulation of P300/CBP-Associated Factor Protects from Vascular Aging via Nrf2 Signal Pathway Activation.International journal of molecular sciences · 2022Article
- KAT2B is an immune infiltration-associated biomarker predicting prognosis and response to immunotherapy in non-small cell lung cancer.Investigational new drugs · 2022Article
- Acute oral toxicity of damnacanthal and its anticancer activity against colorectal tumorigenesis.Toxicology reports · 2022Article
- Recent Updates on Mechanisms of Resistance to 5-Fluorouracil and Reversal Strategies in Colon Cancer Treatment.Biology · 2021Review
- Epigenetic Alterations Upstream and Downstream of p53 Signaling in Colorectal Carcinoma.Cancers · 2021Review
- Targeting Histone Modifications in Bone and Lung Metastatic Cancers.Current osteoporosis reports · 2021Review
- Anacardic Acids fromMolecules (Basel, Switzerland) · 2021Article
- Nanomedicine to Overcome Multidrug Resistance Mechanisms in Colon and Pancreatic Cancer: Recent Progress.Cancers · 2021Review
- The Biological Significance of Targeting Acetylation-Mediated Gene Regulation for Designing New Mechanistic Tools and Potential Therapeutics.Biomolecules · 2021Review
- Carnosol Is a Novel Inhibitor of p300 Acetyltransferase in Breast Cancer.Frontiers in oncology · 2021Article
- Acetylation in Tumor Immune Evasion Regulation.Frontiers in pharmacology · 2021Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Only 10%-20% of colorectal cancer (CRC) patients observe effective responses to 5-fluorouracil (5-FU) based chemo-treatment. We used real-time PCR array and Western blot analysis to examine the expression alteration of acetyltransferases and deacetylases in 5-FU resistant CRC cell lines as compared to their respective parental CRC cell lines. Unlike other acetyltransferases and deacetylases, we found that the expression of acetyltransferase P300/CBP-associated factor (PCAF) is consistently decreased in three 5-FU resistant CRC cell lines. Similarly, knockdown of PCAF in HCT116 CRC parental cell line also increases the resistance to 5-FU and attenuates 5-FU-induced apoptosis. Mechanistically, we demonstrated that increased binding of trimethylated histone H3K27 in the promoter region of PCAF attenuated its transcription in 5-FU resistant HCT116/5-FU cells. Decreased PCAF impairs the acetylation of p53 and attenuates the p53-dependent transcription of p21, which results in the increased cyclin D1 and phosphorylation of Retinoblastoma 1. Conversely, overexpression of PCAF in CRC cell lines increases p21 and their susceptibility to 5-FU in vitro and in vivo. However, knockdown of p21 abolishes the beneficial effects of PCAF overexpression on increasing the sensitivity of HCT116/5-FU cells to 5-FU. Also, the reduced intensity of PCAF immunostaining was observed in the precancerous lesion, and microarray data from the public database further demonstrated the association between PCAF down-regulation and poor survival outcome. Our data suggest that PCAF-mediated p53 acetylation is an essential regulatory mechanism for increasing the susceptibility of CRC to 5-FU.
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Registered trials
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