ArticleCancer discovery2026
Serotonin Modulates Lineage Plasticity in Neuroendocrine Prostate Cancer via Epigenetic Reprogramming.
Article in Cancer discovery, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
5 citing papers in PubMed.
- SLC22A3/OCT3 drives serotonin-mediated stemness in pancreatic cancer.Cell reports · 2026Article
- Neurotransmitters in cancer: how receptor signaling and posttranslational modifications modulate tumor progression and offer new therapeutic targets.Cell communication and signaling : CCS · 2026Review
- Beyond neurotransmission: the roles of serotonylation in physiological and pathological processes.Cellular & molecular biology letters · 2026Review
- Quinone reductase 2bioRxiv : the preprint server for biology · 2026Article
- Advances in understanding the tumor microenvironment of neuroendocrine prostate cancer.Frontiers in oncology · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
30 authors.
Funding
Abstract
Neuroendocrine prostate cancer (NEPC) is an aggressive, therapy-resistant subtype of prostate cancer characterized by lineage plasticity. Although metabolic and signaling molecules are increasingly recognized as modulators of tumor progression, their role in cell fate transition remains unclear. NE (neuroendocrine) tumors produce and accumulate serotonin, a neurotransmitter that regulates diverse physiologic processes. In this study, we identify a tumor-intrinsic serotonin axis as a key driver of NEPC lineage commitment and progression. NEPC endogenously synthesizes serotonin via aromatic L-amino acid decarboxylase (AADC; encoded by DDC) and reuptakes it through the transporter SLC6A4. Mechanistically, high levels of intracellular serotonin promote histone serotonylation at H3K4me3Q5, reconfiguring the H3K4me3 chromatin landscape and downstream gene expression, which drives NE differentiation and is associated with suppressed androgen receptor signaling. Pharmacologic inhibition of serotonin synthesis using the FDA-approved DDC inhibitor carbidopa significantly impairs tumor growth and prolongs survival in both genetically engineered and patient-derived xenograft models, highlighting histone serotonylation as a druggable vulnerability in NEPC. SIGNIFICANCE: Collectively, our findings uncover an epigenetically embedded, serotonin-driven lineage program in NEPC, coupling tumor-intrinsic serotonin metabolism with tumor cell fate control, and identify histone serotonylation as a tractable therapeutic vulnerability in lineage-plastic 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.