ArticleCell death & disease2018
Down-regulation of a pro-apoptotic pathway regulated by PCAF/ADA3 in early stage gastric cancer.
Article in Cell death & disease, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 27 citations in OpenAlex.
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- Analysis of Antiangiogenic Potential and Cell Death Mechanism of a Kinetically Inert Platinum Antitumor Agent.ACS medicinal chemistry letters · 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
- Gastric Cancer in the Era of Epigenetics.International journal of molecular sciences · 2024Review
- Cell-free circulating tumor RNAs in plasma as the potential prognostic biomarkers in colorectal cancer.Frontiers in oncology · 2023Article
- Article
- Molecular Basis of the Schuurs-Hoeijmakers Syndrome: What We Know about the Gene and the PACS-1 Protein and Novel Therapeutic Approaches.International journal of molecular sciences · 2022Review
- Acetylation in Tumor Immune Evasion Regulation.Frontiers in pharmacology · 2021Review
- Upregulation of COL8A1 indicates poor prognosis across human cancer types and promotes the proliferation of gastric cancer cells.Oncology letters · 2020Article
- WISP1 indicates poor prognosis and regulates cell proliferation and apoptosis in gastric cancer via targeting AKT/mTOR signaling pathway.American journal of translational research · 2020Article
- Identification of Prognostic Markers in Cholangiocarcinoma Using Altered DNA Methylation and Gene Expression Profiles.Frontiers in genetics · 2020Article
- Comprehensive Analysis of the Expression, Relationship to Immune Infiltration and Prognosis of TIM-1 in Cancer.Frontiers in oncology · 2020Article
- Targeting epigenetic regulators for cancer therapy: mechanisms and advances in clinical trials.Signal transduction and targeted therapyReview
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The loss of p300/CBP-associated protein (PCAF) expression is associated with poor clinical outcome in gastric cancer, and a potential bio-marker for invasive and aggressive tumors. However, the mechanism linking loss of PCAF to the onset of gastric cancer has not been identified. Given that PCAF and its binding partner transcriptional adaptor protein 3 (ADA3) were recently shown to regulate the intrinsic (mitochondrial) pathway to apoptosis via epigenetic regulation of phosphofurin acidic cluster sorting proteins 1 and 2 (PACS1, PACS2), we analyzed PCAF, ADA3, and PACS1/2 expression in 99 patient-matched surgical samples ranging from normal gastric mucosa, through pre-malignant chronic gastritis and intestinal metaplasia to stage I-III invasive cancers. PCAF mRNA levels were not reduced in either pre-malignant state but were significantly down-regulated in all stages of gastric cancer, commencing at AJCC stage I (p < 0.05), thus linking reduced PCAF expression with early malignant change. Furthermore, patients with combined reduction of PCAF and PACS1 had significantly poorer overall survival (p = 0.0257), confirmed in an independent dataset of 359 patients (p = 5.8 × 10e-6). At the protein level, PCAF, ADA3, and PACS1 expression were all significantly down-regulated in intestinal-type gastric cancer, and correlated with reduced progression free survival. We conclude that a pro-apoptotic mechanism centered on the intrinsic (mitochondrial) pathway and regulated by PCAF/ADA3 can influence the progression from premalignant to malignant change, and thus act as a tumor suppression mechanism in gastric cancer.
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