ArticleJCI insight2023
LSD1 promotes prostate cancer reprogramming by repressing TP53 signaling independently of its demethylase function.
Article in JCI insight, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 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
36 citing papers in PubMed, 37 citations in OpenAlex.
- Cell plasticity in cancer and therapy resistance.Experimental & molecular medicine · 2026Review
- Systematic analysis of hippo pathway signaling identifies TEAD1 as a transcriptional regulator of neuroendocrine prostate cancer.Neoplasia (New York, N.Y.) · 2026Article
- Genomic Determinants of Lethality and Therapeutic Vulnerability in Castration-Resistant Prostate Cancer.bioRxiv : the preprint server for biology · 2026Article
- Targeting lysine-specific demethylase 1 inhibits melanoma metastasis via the NF2-Hippo-YAP pathway.Cell death & disease · 2026Article
- Exploiting tumor lineage features for precision cancer therapy.Trends in cancer · 2026Review
- Comparative analysis for optimal LSD1 inhibitors evaluation techniques: pros and cons.Journal of pharmaceutical analysis · 2026Review
- Review
- SMARCA4 promotes lineage plasticity and enzalutamide resistance in prostate cancer by regulating PROX1 via H3K27 acetylation.Cell death discovery · 2026Article
- KDM7A and KDM1A inhibition suppresses tumour promoting pathways in prostate cancer.Molecular oncology · 2026Article
- LSD1 Performs Demethylase-Independent and Context-Specific Roles in Ewing Sarcoma.Cancer research communications · 2026Article
- Genetic and epigenetic mechanisms underlying treatment-induced neuroendocrine prostate cancer.Journal of the National Cancer Center · 2026Review
- Transcriptional and epigenetic reprogramming, lineage plasticity and therapy resistance in prostate cancer.Journal of the National Cancer Center · 2026Review
- KDM4A promotes NEPC progression through regulation of MYC expression.Cancer letters · 2026Article
- RUNX1T1 drives stem-like small-cell neuroendocrine prostate cancer identity.Frontiers in cell and developmental biology · 2026Article
- LSD1 Performs Demethylase-Independent and Context-Specific Roles in Ewing Sarcoma.bioRxiv : the preprint server for biology · 2025Article
- Review
- Mechanisms of neuroendocrine differentiation in castration-resistant prostate cancer and advances in the treatment of neuroendocrine prostate cancer.Annals of medicine · 2025Review
- Precision epigenetic therapies in oncology.Cancer metastasis reviews · 2025Review
- New frontiers in prostate cancer treatment from systemic therapy to targeted therapy.EMBO molecular medicine · 2025Review
- Widespread activation and critical role of EMT and stemness in the neuroendocrine differentiation of prostate cancer (Review).Oncology reports · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
25 authors at 5 institutions in 3 countries.
Funding
Abstract
Lysine-specific demethylase 1 (LSD1) is a histone demethylase that promotes stemness and cell survival in cancers such as prostate cancer. Most prostate malignancies are adenocarcinomas with luminal differentiation. However, some tumors undergo cellular reprogramming to a more lethal subset termed neuroendocrine prostate cancer (NEPC) with neuronal differentiation. The frequency of NEPC is increasing since the widespread use of potent androgen receptor signaling inhibitors. Currently, there are no effective treatments for NEPC. We previously determined that LSD1 promotes survival of prostate adenocarcinoma tumors. However, the role of LSD1 in NEPC is unknown. Here, we determined that LSD1 is highly upregulated in NEPC versus adenocarcinoma patient tumors. LSD1 suppression with RNAi or allosteric LSD1 inhibitors - but not catalytic inhibitors - reduced NEPC cell survival. RNA-Seq analysis revealed that LSD1 represses pathways linked to luminal differentiation, and TP53 was the top reactivated pathway. We confirmed that LSD1 suppressed the TP53 pathway by reducing TP53 occupancy at target genes while LSD1's catalytic function was dispensable for this effect. Mechanistically, LSD1 inhibition disrupted LSD1-HDAC interactions, increasing histone acetylation at TP53 targets. Finally, LSD1 inhibition suppressed NEPC tumor growth in vivo. These findings suggest that blocking LSD1's noncatalytic function may be a promising treatment strategy for NEPC.
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What Socratic holds
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 Socratic graph.