ArticleLaboratory investigation; a journal of technical methods and pathology2018
Adenylosuccinate lyase enhances aggressiveness of endometrial cancer by increasing killer cell lectin-like receptor C3 expression by fumarate.
Article in Laboratory investigation; a journal of technical methods and pathology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 30 citations in OpenAlex.
- ADSL drives fumarate mediated scrib-rictor complex formation to promote metastasis dissemination in triple-negative breast cancer.Molecular cancer · 2026Article
- Adenylosuccinate lyase in pancreatic ductal adenocarcinoma chemoresistance: from purine metabolism to metabolic vulnerability.Cancer drug resistance (Alhambra, Calif.) · 2026Review
- Development of Cell-Permeable Adenylosuccinate Lyase Inhibitor.Methods and protocols · 2025Article
- The Landscape of Cancer Metabolism as a Therapeutic Target.Pathology international · 2025Review
- Molecular mechanism of tumor-infiltrating immune cells regulating endometrial carcinoma.Genes & diseases · 2025Review
- Investigating the relevance of nucleotide metabolism in the prognosis of glioblastoma through bioinformatics models.Scientific reports · 2025Article
- Interplay between mTOR and Purine Metabolism Enzymes and Its Relevant Role in Cancer.International journal of molecular sciences · 2024Review
- The prevalence of ADSL (rs3788579) and CYP1A2 (rs17861162) polymorphisms in female breast cancer patients in North-West Iran.Discover oncology · 2024Article
- Can the reprogrammed cancer cells serve as an alternative source of (induced) cancer stem cells?Reports of practical oncology and radiotherapy : journal of Greatpoland Cancer Center in Poznan and Polish Society of Radiation Oncology · 2024Article
- Silencing of Dicer enhances dacarbazine resistance in melanoma cells by inhibiting ADSL expression.Aging · 2023Article
- Role of mitochondrial alterations in human cancer progression and cancer immunity.Journal of biomedical science · 2023Review
- Review
- Carcinogenic effect of adenylosuccinate lyase (ADSL) in prostate cancer development and progression through the cell cycle pathway.Cancer cell international · 2021Article
- A Metabolic Model of Intestinal Secretions: The Link between Human Microbiota and Colorectal Cancer Progression.Metabolites · 2021Article
- Targeting the De Novo Purine Synthesis Pathway Through Adenylosuccinate Lyase Depletion Impairs Liver Cancer Growth by Perturbing Mitochondrial Function.Hepatology (Baltimore, Md.) · 2021Article
- Targeting Mitochondrial Oncometabolites: A New Approach to Overcome Drug Resistance in Cancer.Pharmaceutics · 2021Review
- Article
- Review
- iMAP: A Web Server for Metabolomics Data Integrative Analysis.Frontiers in chemistry · 2021Article
- Adenylosuccinate lyase is oncogenic in colorectal cancer by causing mitochondrial dysfunction and independent activation of NRF2 and mTOR-MYC-axis.Theranostics · 2021Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adenylosuccinate lyase (ADSL) is an enzyme that plays important roles in de novo purine synthesis. Although ADSL was reported to be upregulated in various malignancies, such as colorectal, breast, and prostate cancer, as well as gliomas, the mechanism by which elevated ADSL expression contributes to cancer has not been elucidated. We previously performed a shotgun proteomics analysis to characterize specific proteins associated with the properties of the aldehyde dehydrogenase (ALDH)-high cell population, which was reported to be involved in tumorigenic potential, and showed that ADSL expression is upregulated in the ALDH-high population of endometrial cancer. Here, we showed that ADSL is involved in endometrial cancer aggressiveness by regulating expression of killer cell lectin-like receptor C3 (KLRC3), which is a receptor expressed on natural killer cells. Immunohistochemical analysis indicated that ADSL expression increased as endometrioid carcinoma specimens became more poorly differentiated and higher degree of primary tumor progression. Knockdown of ADSL in endometrial cancer cells decreased cell proliferation, migration, and invasive capability, and caused the cells to adopt a more rounded shape. DNA microarray analysis and quantitative real-time PCR showed that KLRC3 expression was decreased in ADSL knockdown cells. Knockdown of KLRC3 in endometrial cancer cells resulted in the same phenotype as knockdown of ADSL. Moreover, fumarate, which could be produced by ADSL and was recently shown to be an oncometabolite, recovered KLRC3 expression in ADSL knockdown cells, suggesting that fumarate produced by ADSL could regulate KLRC3 expression. Our findings indicate that ADSL enhances cell proliferation, migration, and invasive capability through regulation of KLRC3 expression by fumarate.
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