ArticleClinical and translational medicine2022
The central role of Sphingosine kinase 1 in the development of neuroendocrine prostate cancer (NEPC): A new targeted therapy of NEPC.
Article in Clinical and translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 23 citations in OpenAlex.
- IGFBP3-SphK1/S1P Signaling Axis Drives Enzalutamide Resistance in Advanced Prostate Cancer.Molecular cancer therapeutics · 2026Article
- Clonal selection of pre-existing neuroendocrine component in prostate cancer during androgen receptor signaling inhibitor therapy: A case report.Urology case reports · 2026Article
- Advances in understanding the tumor microenvironment of neuroendocrine prostate cancer.Frontiers in oncology · 2026Review
- Widespread activation and critical role of EMT and stemness in the neuroendocrine differentiation of prostate cancer (Review).Oncology reports · 2025Review
- Integrating anamnestic and lifestyle data with sphingolipid levels for risk-based prostate cancer screening.Journal of translational medicine · 2025Observational
- The value of MRI-based radiomics and clinicoradiological data for the detection of forkhead box protein A1 gene mutated prostate cancer.Scientific reports · 2025Article
- Identification of the specific characteristics of neuroendocrine prostate cancer: Immune status, hub genes and treatment.Translational oncology · 2025Article
- New Insights into Potential Therapeutic Targets for Neuroendocrine Prostate Cancer: From Bench to Clinic.Research (Washington, D.C.) · 2025Review
- Identification of BIRC5 and HMMR as prognostic biomarkers for immune infiltration in prostate cancer.Translational andrology and urology · 2024Article
- SPHK1 promotes bladder cancer metastasis via PD-L2/c-Src/FAK signaling cascade.Cell death & disease · 2024Article
- Treatment-induced neuroendocrine prostate cancer andWorld journal of clinical cases · 2024Article
- Subtype Transdifferentiation in Human Cancer: The Power of Tissue Plasticity in Tumor Progression.Cells · 2024Review
- Lysosome-dependent FOXA1 ubiquitination contributes to luminal lineage of advanced prostate cancer.Molecular oncology · 2023Article
- Targeting Key Players of Neuroendocrine Differentiation in Prostate Cancer.International journal of molecular sciences · 2023Review
- Targeting Sphingosine 1-Phosphate Metabolism as a Therapeutic Avenue for Prostate Cancer.Cancers · 2023Review
- A Theranostic Small-Molecule Prodrug Conjugate for Neuroendocrine Prostate Cancer.Pharmaceutics · 2023Article
- Developing New Treatment Options for Castration-Resistant Prostate Cancer and Recurrent Disease.Biomedicines · 2022Review
- The central role of Sphingosine kinase 1 in the development of neuroendocrine prostate cancer (NEPC): A new targeted therapy of NEPC.Clinical and translational medicine · 2022Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
backgroundNeuroendocrine prostate cancer (NEPC) is often diagnosed as a sub-type from the castration-resistant prostate cancer (CRPC) recurred from the second generation of anti-androgen treatment and is a rapidly progressive fatal disease. The molecular mechanisms underlying the trans-differentiation from CRPC to NEPC are not fully characterized, which hampers the development of effective targeted therapy.
methodsBioinformatic analyses were conducted to determine the clinical correlation of sphingosine kinase 1 (SphK1) in CRPC progression. To investigate the transcriptional regulation SphK1 and neuroendocrine (NE) transcription factor genes, both chromosome immunoprecipitation and luciferase reporter gene assays were performed. To demonstrate the role of SphK1 in NEPC development, neurosphere assay was carried out along with several biomarkers determined by quantitative PCR and western blot. Furthermore, in vivo NEPC xenograft models and patient-derived xenograft (PDX) model were employed to determine the effect of SphK1 inhibitors and target validation.
resultsSignificant prevalence of SphK1 in NEPC development is observed from clinical datasets. SphK1 is transcriptionally repressed by androgen receptor-RE1-silencing transcription factor (REST) complex. Furthermore, sphingosine 1-phosphate produced by SphK1 can modulate REST protein turnover via MAPK signaling pathway. Also, decreased REST protein levels enhance the expression of NE markers in CRPC, enabling the transition to NEPC. Finally, specific SphK1 inhibitors can effectively inhibit the growth of NEPC tumors and block the REST protein degradation in PDX.
conclusionsSphK1 plays a central role in NEPC development, which offers a new target for this lethal cancer using clinically approved SphK1 inhibitors.
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