ArticleCancers2021
Blockade of AMPK-Mediated cAMP-PKA-CREB/ATF1 Signaling Synergizes with Aspirin to Inhibit Hepatocellular Carcinoma.
Article in Cancers, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 2 of them syntheses that pooled it.
What it found
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 2 syntheses or guidelines pooled it, 36 citations in OpenAlex.
- Aspirin in Patients with Viral Hepatitis: Systematic Review and Meta-Analysis of Observational Studies.Journal of gastrointestinal cancer · 2024Pooled it
- Looking at NSAIDs from a historical perspective and their current status in drug repurposing for cancer treatment and prevention.Journal of cancer research and clinical oncology · 2023Pooled it
- CPS1 promotes colorectal cancer progression by inducing EMT and activating TGF-β/Smad signaling pathway.iScience · 2026Article
- Potential of RAD51C as a hub gene and therapeutic target in bladder cancer: insights from bioinformatics and experimental analysis.International journal of surgery (London, England) · 2026Article
- Reprogramming of nitrogen metabolism in tumors: mechanisms and therapeutic implications.Amino acids · 2026Review
- The Prognostic Value of CIP2A and Its Association with CD31, E-Cadherin, and pAMPK in Lung Cancer.International journal of molecular sciences · 2025Article
- CPS1-promoted the progression of lung adenocarcinoma via suppressing ammonia induced the activation of ROS/AMPK/P53/LKB1 signaling pathway.Scientific reports · 2025Article
- Integrating network pharmacology, quantitative transcriptomic analysis, and experimental validation revealed the mechanism of cordycepin in the treatment of obesity.Frontiers in pharmacology · 2025Article
- ATF1 regulates MAL2 expression through inhibition of miR-630 to mediate the EMT process that promotes cervical cancer cell development and metastasis.Journal of gynecologic oncology · 2025Article
- Aspirin in Cancer Therapy: Pharmacology and Nanotechnology Advances.International journal of nanomedicine · 2025Review
- cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment.Journal of hematology & oncology · 2024Review
- MFG-E8 promotes M2 polarization of macrophages and is associated with poor prognosis in patients with gastric cancer.Heliyon · 2024Article
- Will AMPK be a potential therapeutic target for hepatocellular carcinoma?American journal of cancer research · 2024Review
- Identification of ACBD3 as a new molecular biomarker in pan-cancers through bioinformatic analysis: a preclinical study.European journal of medical research · 2023Article
- Synergistic antitumor efficacy of aspirin plus lenvatinib in hepatocellular carcinoma via regulating of diverse signaling pathways.Cell death discovery · 2023Article
- ATF1 promotes the malignancy of lung adenocarcinoma cells by transcriptionally regulating ZNF143 expression.Acta biochimica et biophysica Sinica · 2023Article
- Xihuang pill induces pyroptosis and inhibits progression of breast cancer cells via activating the cAMP/PKA signalling pathway.American journal of cancer research · 2023Article
- MiR-942-5p inhibits tumor migration and invasion through targeting CST1 in esophageal squamous cell carcinoma.PloS one · 2023Article
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Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Aspirin can prevent or inhibit inflammation-related cancers, such as colorectal cancer and hepatocellular carcinoma (HCC). However, the effectiveness of chemotherapy may be compromised by activating oncogenic pathways in cancer cells. Elucidation of such chemoresistance mechanisms is crucial to developing novel strategies to maximize the anti-cancer effects of aspirin. Here, we report that aspirin markedly induces CREB/ATF1 phosphorylation in HCC cells, which compromises aspirin's anti-HCC effect. Inhibition of AMP-activated protein kinase (AMPK) abrogates the induction of CREB/ATF1 phosphorylation by aspirin. Mechanistically, activation of AMPK by aspirin results in decreased expression of the urea cycle enzyme carbamoyl-phosphate synthase 1 (CPS1) in HCC cells and xenografts. Treatment with aspirin or CPS1 knockdown stimulates soluble adenylyl cyclase expression, thereby increasing cyclic AMP (cAMP) synthesis and stimulating PKA-CREB/ATF1 signaling. Importantly, abrogation of aspirin-induced CREB/ATF1 phosphorylation could sensitize HCC to aspirin. The bis-benzylisoquinoline alkaloid berbamine suppresses the expression of cancerous inhibitor of protein phosphatase 2A (CIP2A), leading to protein phosphatase 2A-mediated downregulation of CREB/ATF1 phosphorylation. The combination of berbamine and aspirin significantly inhibits HCC in vitro and in vivo. These data demonstrate that the regulation of cAMP-PKA-CREB/ATF1 signaling represents a noncanonical function of CPS1. Targeting the PKA-CREB/ATF1 axis may be a strategy to improve the therapeutic effects of aspirin on HCC.
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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.