ArticleProceedings of the National Academy of Sciences of the United States of America2009
Identification of genes conferring resistance to 5-fluorouracil.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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.
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Who cites it
88 citing papers in PubMed, 140 citations in OpenAlex.
- Molecular Pathophysiology of Hepatocellular Carcinoma: From Metabolic Inflammation to Therapeutic Targets.Cancers · 2026Review
- Review
- USP7 promotes cervical cancer progression by stabilizing MTDH expression through deubiquitination.Journal of cancer research and clinical oncology · 2024Article
- Personalizing adjuvant therapy for patients with colorectal cancer.Nature reviews. Clinical oncology · 2024Review
- Astrocyte Elevated Gene-1 Cys75Biochemistry · 2023Article
- MALAT1-miRNAs network regulate thymidylate synthase and affect 5FU-based chemotherapy.Molecular medicine (Cambridge, Mass.) · 2022Review
- Emerging Role and Clinicopathological Significance of AEG-1 in Different Cancer Types: A Concise Review.Cells · 2021Review
- Multifunctional Role of Astrocyte Elevated Gene-1 (AEG-1) in Cancer: Focus on Drug Resistance.Cancers · 2021Review
- The Scope of Astrocyte Elevated Gene-1/Metadherin (AEG-1/MTDH) in Cancer Clinicopathology: A Review.Genes · 2021Review
- Overexpression of microRNA-124-5p sensitizes non-small cell lung cancer cells to treatment with 5-fluorouracil via AEG-1 regulation.Oncology letters · 2021Article
- Astrocyte elevated gene-1 (AEG-1): A key driver of hepatocellular carcinoma (HCC).Advances in cancer research · 2021Review
- Article
- Mucinous adenocarcinoma is a pharmacogenomically distinct subtype of colorectal cancer.The pharmacogenomics journal · 2020Review
- A non-proliferative role of pyrimidine metabolism in cancer.Molecular metabolism · 2020Review
- Metadherin-PRMT5 complex enhances the metastasis of hepatocellular carcinoma through the WNT-β-catenin signaling pathway.Carcinogenesis · 2020Article
- Identification of a 3,3-difluorinated tetrahydropyridinol compound as a novel antitumor agent for hepatocellular carcinoma acting via cell cycle arrest through disturbing CDK7-mediated phosphorylation of Cdc2.Investigational new drugs · 2020Article
- Dihydropyrimidinase protects from DNA replication stress caused by cytotoxic metabolites.Nucleic acids research · 2020Article
- Metadherin enhances vulnerability of cancer cells to ferroptosis.Cell death & disease · 2019Article
- Exosomal transfer of p-STAT3 promotes acquired 5-FU resistance in colorectal cancer cells.Journal of experimental & clinical cancer research : CR · 2019Article
- TYMS/KRAS/BRAF molecular profiling predicts survival following adjuvant chemotherapy in colorectal cancer.World journal of gastrointestinal oncology · 2019Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Astrocyte elevated gene-1 (AEG-1) is overexpressed in >90% of human hepatocellular carcinoma (HCC) patients and plays a significant role in mediating aggressive progression of HCC. AEG-1 is known to augment invasion, metastasis, and angiogenesis, and we now demonstrate that AEG-1 directly contributes to another important hallmark of aggressive cancers, that is, resistance to chemotherapeutic drugs, such as 5-fluorouracil (5-FU). AEG-1 augments expression of the transcription factor LSF that regulates the expression of thymidylate synthase (TS), a target of 5-FU. In addition, AEG-1 enhances the expression of dihydropyrimidine dehydrogenase (DPYD) that catalyzes the initial and rate-limiting step in the catabolism of 5-FU. siRNA-mediated inhibition of AEG-1, LSF, or DPYD significantly increased the sensitivity of HCC cells to 5-FU in vitro and a lentivirus delivering AEG-1 siRNA in combination with 5-FU markedly inhibited growth of HCC cells xenotransplanted in athymic nude mice when compared to either agent alone. The present studies highlight 2 previously unidentified genes, AEG-1 and LSF, contributing to chemoresistance. Inhibition of AEG-1 might be exploited as a therapeutic strategy along with 5-FU-based combinatorial chemotherapy for HCC, a highly fatal cancer with currently very limited therapeutic options.
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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.