ArticleInternational journal of cancer2012
Acid ceramidase-mediated production of sphingosine 1-phosphate promotes prostate cancer invasion through upregulation of cathepsin B.
Article in International journal of cancer, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 70 citations in OpenAlex.
- Sphingolipids in human disease: organ-specific pathologies, chain-length-dependent effects, and translational implications.Journal of translational medicine · 2026Review
- HPLC-HRMS and interpretable machine learning decipher serum lipidomic signatures in NSCLC.PeerJ · 2026Article
- The mycotoxin Beauvericin is an uncompetitive inhibitor of Cathepsin B.Protein science : a publication of the Protein Society · 2025Article
- Cathepsin B in urological tumors: unraveling its role and therapeutic potential.Discover oncology · 2025Review
- Vitamin C-Dependent Uptake of Non-Heme Iron by Enterocytes, Its Impact on Erythropoiesis and Redox Capacity of Human Erythrocytes.Antioxidants (Basel, Switzerland) · 2024Review
- Association between cathepsins and benign prostate diseases: a bidirectional two-sample Mendelian randomization study.Frontiers in endocrinology · 2024Article
- Inhibitory effect of Porphyromonas gingivalis-derived phosphoethanolamine dihydroceramide on acid ceramidase expression in oral squamous cells.Journal of cellular and molecular medicine · 2023Article
- The Effect of Silencing the Genes Responsible for the Level of Sphingosine-1-phosphate on the Apoptosis of Colon Cancer Cells.International journal of molecular sciences · 2023Article
- Acid ceramidase targeting pyruvate kinase affected trypsinogen activation in acute pancreatitis.Molecular medicine (Cambridge, Mass.) · 2022Article
- Article
- Sphingolipid metabolism in the development and progression of cancer: one cancer's help is another's hindrance.Molecular oncology · 2021Review
- Autophagy provides a conceptual therapeutic framework for bone metastasis from prostate cancer.Cell death & disease · 2021Review
- RNA interference mediated suppression of TRPV6 inhibits the progression of prostate cancerInvestigative and clinical urology · 2021Article
- Role of SPTSSB-Regulated de Novo Sphingolipid Synthesis in Prostate Cancer Depends on Androgen Receptor Signaling.iScience · 2020Article
- Functional Lipids in Autoimmune Inflammatory Diseases.International journal of molecular sciences · 2020Review
- Identification of radiation responsive genes and transcriptome profiling via complete RNA sequencing in a stable radioresistant U87 glioblastoma model.Oncotarget · 2018Article
- Loss of acid ceramidase in myeloid cells suppresses intestinal neutrophil recruitment.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Novel Sphingolipid-Based Cancer Therapeutics in the Personalized Medicine Era.Advances in cancer research · 2018Review
- Interdiction of Sphingolipid Metabolism Revisited: Focus on Prostate Cancer.Advances in cancer research · 2018Review
- Contribution of Adipose Tissue to Development of Cancer.Comprehensive Physiology · 2017Review
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
Abstract
Invasiveness is one of the key features of aggressive prostate cancer; however, our understanding of the precise mechanisms effecting invasion remains limited. The ceramide hydrolyzing enzyme acid ceramidase (AC), overexpressed in most prostate tumors, causes an aggressive and invasive phenotype through downstream effectors that have not yet been well characterized. Here, we demonstrate that AC, through generation of sphingosine-1-phosphate (S1P), promotes Ets1 nuclear expression and binding to the promoter region of matrix-degrading protease cathepsin B. Through confocal microscopy and flow cytometry, we found that AC overexpression promotes pericellular localization of cathepsin B and its translocation to the outer leaflet of the cell membrane. AC overexpressing cells have an increased abundance of cathepsin B-enriched invasive structures and enhanced ability to invade through a collagen matrix, but not in the presence of an inhibitor of cathepsin B. In human prostate tissues, AC and cathepsin B overexpression were strongly associated and may relate to poor outcome. These results demonstrate a novel pathway by which AC, through S1P, promotes an invasive phenotype in prostate cancer by causing overexpression and secretion of cathepsin B through activation and nuclear expression of Ets1. As prostate cancer prognosis is dramatically worse when invasion has occurred, this study provides critical insight into the progression toward lethal prostate cancer.
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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.