ArticleCell death and differentiation2012
Plasma membrane-associated sialidase (NEU3) regulates progression of prostate cancer to androgen-independent growth through modulation of androgen receptor signaling.
Article in Cell death and differentiation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed.
- Ganglioside GM3 in the Tumor Microenvironment: Mechanisms of Signaling Regulation and Strategies for Angiogenesis Inhibition.Biomolecules · 2026Review
- Decoding sialidase: physiological roles, pathological pathways, and clinical opportunities.Frontiers in cellular and infection microbiology · 2026Review
- Degradation System: Sialidase.Methods in molecular biology (Clifton, N.J.) · 2026Article
- The Ying and Yang of Ganglioside Function in Cancer.Cancers · 2023Review
- Inhibitors of the Sialidase NEU3 as Potential Therapeutics for Fibrosis.International journal of molecular sciences · 2022Review
- Sialidase NEU3 and its pathological significance.Glycoconjugate journal · 2022Review
- Review
- Sphingolipid metabolism in the development and progression of cancer: one cancer's help is another's hindrance.Molecular oncology · 2021Review
- KLF9 suppresses cell growth and induces apoptosis via the AR pathway in androgen-dependent prostate cancer cells.Biochemistry and biophysics reports · 2021Article
- Serum Sialylation Changes in Actinic Keratosis and Cutaneous Squamous Cell Carcinoma Patients.Journal of personalized medicine · 2021Article
- Neu3 neuraminidase induction triggers intestinal inflammation and colitis in a model of recurrent human food-poisoning.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Gangliosides as Signaling Regulators in Cancer.International journal of molecular sciences · 2021Review
- Inhibiting Sialidase-Induced TGF-The Journal of pharmacology and experimental therapeutics · 2021Article
- HILIC-MRM-MS for Linkage-Specific Separation of Sialylated Glycopeptides to Quantify Prostate-Specific Antigen Proteoforms.Journal of proteome research · 2020Article
- Article
- Attenuated pulmonary fibrosis in sialidase-3 knockout (American journal of physiology. Lung cellular and molecular physiology · 2020Article
- Comprehensive Profiling of Surface Gangliosides Extracted from Various Cell Lines by LC-MS/MS.Cells · 2019Article
- Serum sialylation changes in cancer.Glycoconjugate journal · 2018Review
- Deregulation of sialidases in human normal and tumor tissues.Cancer biomarkers : section A of Disease markers · 2018Article
- Recurrent infection progressively disables host protection against intestinal inflammation.Science (New York, N.Y.) · 2017Article
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Authors and funding
15 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Prostate cancers generally become androgen-independent and resistant to hormone therapy with progression. To understand the underlying mechanisms and facilitate the development of novel treatments for androgen-independent prostate cancer, we have investigated plasma membrane-associated sialidase (NEU3), the key enzyme for ganglioside hydrolysis participating in transmembrane signaling. We have discovered NEU3 to be upregulated in human prostate cancer compared with non-cancerous tissue, correlating with the Gleason score. NEU3 silencing with siRNA in prostate cancer PC-3 and LNCaP cells resulted in increased expression of differentiation markers and in cell apoptosis, but decrease in Bcl-2 as well as a progression-related transcription factor, early growth response gene (EGR-1). In androgen-sensitive LNCaP cells, forced overexpression of NEU3 significantly induced expression of EGR-1, androgen receptor (AR) and PSA both with and without androgen, the cells becoming sensitive to androgen. The NEU3-mediated induction was abrogated by inhibitors for PI-3 kinase and MAP kinase and more specifically by their silencing in the absence of androgen, being confirmed by increased phosphorylation of AKT and ERK1/2 in NEU3 overexpressing cells. NEU3 siRNA introduction caused reduction of cell growth of an androgen-independent PC-3 cells in culture and of transplanted tumors in nude mice. These data suggest that NEU3 regulates tumor progression through AR signaling, and thus be a potential tool for diagnosis and therapy of androgen-independent prostate cancer.
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