ArticleNature communications2020
Androgen deprivation upregulates SPINK1 expression and potentiates cellular plasticity in prostate cancer.
Article in Nature communications, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
What it found
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
51 citing papers in PubMed, 86 citations in OpenAlex.
- DKC1 promotes colorectal cancer progression and therapy resistance by dysregulating sphingolipid biosynthesis.Nature communications · 2026Article
- SPINK3-Sperm Interaction Determines a Stable Sperm Subpopulation With Intact CatSper Channel.Journal of cellular physiology · 2026Article
- The role of SOX transcription factors in prostate cancer: Focusing on SOX2.Genes & diseases · 2025Review
- SPINK3-sperm interaction determines a stable sperm subpopulation with intact CatSper channel: SPINK3 stabilizes CatSper1 and membrane.bioRxiv : the preprint server for biology · 2025Article
- Widespread activation and critical role of EMT and stemness in the neuroendocrine differentiation of prostate cancer (Review).Oncology reports · 2025Review
- The SPINK Protein Family in Cancer: Emerging Roles in Tumor Progression, Therapeutic Resistance, and Precision Oncology.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Transcriptional profiling clarifies a program of enzalutamide extreme non-response in lethal prostate cancer.NPJ precision oncology · 2025Article
- New Insights into Potential Therapeutic Targets for Neuroendocrine Prostate Cancer: From Bench to Clinic.Research (Washington, D.C.) · 2025Review
- Examination of the enrichment of neuronal extracellular vesicles from cell conditioned media and human plasma using an anti-NCAM immunocapture bead approach.BMC methods · 2025Article
- KIF1A promotes neuroendocrine differentiation in prostate cancer by regulating the OGT-mediated O-GlcNAcylation.Cell death & disease · 2024Article
- Single-cell analysis reveals alternations between the aged and young mice prostates.Biomarker research · 2024Article
- LARP4B promotes hepatocellular carcinoma progression and impairs sorafenib efficacy by activating SPINK1-mediated EGFR pathway.Cell death discovery · 2024Article
- An integrative proteomics approach identifies tyrosine kinase KIT as a therapeutic target for SPINK1-positive prostate cancer.iScience · 2024Article
- Bridging Health Disparities: a Genomics and Transcriptomics Analysis by Race in Prostate Cancer.Journal of racial and ethnic health disparities · 2024Article
- Neurokinin-1 receptor drives PKCɑ-AURKA/N-Myc signaling to facilitate the neuroendocrine progression of prostate cancer.Cell death & disease · 2023Article
- Androgen deprivation restores ARHGEF2 to promote neuroendocrine differentiation of prostate cancer.Cell death & disease · 2022Article
- Lung transcriptome of nonhuman primates exposed to total- and partial-body irradiation.Molecular therapy. Nucleic acids · 2022Article
- Race and prostate cancer: genomic landscape.Nature reviews. Urology · 2022Review
- Epigenetic reprogramming during prostate cancer progression: A perspective from development.Seminars in cancer biology · 2022Review
- The Role of Human Chorionic Gonadotropin Beta (hCGβ) in HPV-Positive and HPV-Negative Oropharyngeal Squamous Cell Carcinoma.Cancers · 2022Article
Corrections and comments
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Authors and funding
15 authors at 7 institutions in 4 countries.
Funding
Abstract
Emergence of an aggressive androgen receptor (AR)-independent neuroendocrine prostate cancer (NEPC) after androgen-deprivation therapy (ADT) is well-known. Nevertheless, the majority of advanced-stage prostate cancer patients, including those with SPINK1-positive subtype, are treated with AR-antagonists. Here, we show AR and its corepressor, REST, function as transcriptional-repressors of SPINK1, and AR-antagonists alleviate this repression leading to SPINK1 upregulation. Increased SOX2 expression during NE-transdifferentiation transactivates SPINK1, a critical-player for maintenance of NE-phenotype. SPINK1 elicits epithelial-mesenchymal-transition, stemness and cellular-plasticity. Conversely, pharmacological Casein Kinase-1 inhibition stabilizes REST, which in cooperation with AR causes SPINK1 transcriptional-repression and impedes SPINK1-mediated oncogenesis. Elevated levels of SPINK1 and NEPC markers are observed in the tumors of AR-antagonists treated mice, and in a subset of NEPC patients, implicating a plausible role of SPINK1 in treatment-related NEPC. Collectively, our findings provide an explanation for the paradoxical clinical-outcomes after ADT, possibly due to SPINK1 upregulation, and offers a strategy for adjuvant therapies.
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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.