ArticleThe American journal of pathology2012
Integrative molecular profiling reveals asparagine synthetase is a target in castration-resistant prostate cancer.
Article in The American journal of pathology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 81 citations in OpenAlex.
- FAM50A drives breast cancer brain metastasis through interaction with C9ORF78 to enhance ʟ-asparagine production.Science advances · 2025Article
- Targeting Asparagine Metabolism in Solid Tumors.Nutrients · 2025Review
- Ammonium metabolism rewiring in the prostate cancer microenvironment: Mechanisms and clinical prospects.Frontiers in oncology · 2025Review
- Integrated proteomics and metabolomics analyses reveal new insights into the antitumor effects of valproic acid plus simvastatin combination in a prostate cancer xenograft model associated with downmodulation of YAP/TAZ signaling.Cancer cell international · 2024Article
- Asparagine Dependency Is a Targetable Metabolic Vulnerability in TP53-Altered Castration-Resistant Prostate Cancer.Cancer research · 2024Article
- Integrated Bioinformatics Analysis Identified ASNS and DDIT3 as the Therapeutic Target in Castrate-Resistant Prostate Cancer.International journal of molecular sciences · 2024Article
- Development of a ferroptosis-based molecular markers for predicting RFS in prostate cancer patients.Scientific reports · 2023Article
- A Five Glutamine-Associated Signature Predicts Prognosis of Prostate Cancer and Links Glutamine Metabolism with Tumor Microenvironment.Journal of clinical medicine · 2023Article
- Transcriptome analysis reveals effects of leukemogenic SHP2 mutations in biosynthesis of amino acids signaling.Frontiers in oncology · 2023Article
- Biochemical recurrence related metabolic novel signature associates with immunity and ADT treatment responses in prostate cancer.Cancer medicine · 2023Article
- JAG1 Intracellular Domain Enhances AR Expression and Signaling and Promotes Stem-like Properties in Prostate Cancer Cells.Cancers · 2022Article
- PTEN Protein Phosphatase Activity Is Not Required for Tumour Suppression in the Mouse Prostate.Biomolecules · 2022Article
- Biochemical and Biological Evaluation of an L-Asparaginase from Isolated Escherichia coli MF-107 as an Anti-Tumor Enzyme on MCF7 Cell LineIranian biomedical journal · 2022Article
- Metabolomic and Transcriptomic Profiling Identified Significant Genes in Thymic Epithelial Tumor.Metabolites · 2022Article
- Article
- Mesenchymal and stem-like prostate cancer linked to therapy-induced lineage plasticity and metastasis.Cell reports · 2022Article
- Predictive markers for efficiency of the amino-acid deprivation therapies in cancer.Frontiers in medicine · 2022Article
- Article
- Adipocyte-driven unfolded protein response is a shared transcriptomic signature of metastatic prostate carcinoma cells.Biochimica et biophysica acta. Molecular cell research · 2021Article
- A Novel Ferroptosis-Based Molecular Signature Associated with Biochemical Recurrence-Free Survival and Tumor Immune Microenvironment of Prostate Cancer.Frontiers in cell and developmental biology · 2021Article
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
The identification of new and effective therapeutic targets for the lethal, castration-resistant stage of prostate cancer (CRPC) has been challenging because of both the paucity of adequate frozen tissues and a lack of integrated molecular analysis. Therefore, in this study, we performed a genome-wide analysis of DNA copy number alterations from 34 unique surgical CRPC specimens and 5 xenografts, with matched transcriptomic profiling of 25 specimens. An integrated analysis of these data revealed that the asparagine synthetase (ASNS) gene showed a gain in copy number and was overexpressed at the transcript level. The overexpression of ASNS was validated by analyzing other public CRPC data sets. ASNS protein expression, as detected by reverse-phase protein lysate array, was tightly correlated with gene copy number. In addition, ASNS protein expression, as determined by IHC analysis, was associated with progression to a therapy-resistant disease state in TMAs that included 77 castration-resistant and 40 untreated prostate cancer patient samples. Knockdown of ASNS by small-interfering RNAs in asparagine-deprived media led to growth inhibition in both androgen-responsive (ie, LNCaP) and castration-resistant (ie, C4-2B) prostate cancer cell lines and in cells isolated from a CRPC xenograft (ie, MDA PCa 180-30). Together, our results suggest that ASNS is up-regulated in cases of CRPC and that depletion of asparagine using ASNS inhibitors will be a novel strategy for targeting CRPC cells.
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