ArticleStem cells (Dayton, Ohio)2024
Stem cell dynamics and cellular heterogeneity across lineage subtypes of castrate-resistant prostate cancer.
Article in Stem cells (Dayton, Ohio), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 5 citations in OpenAlex.
- Canonical Wnt signaling in the regulation of prostate cancer stem cells: a key driver of castration-resistant prostate cancer and a therapeutic opportunity.Journal of translational medicine · 2026Review
- The YAP1 and EPHA3 receptor tyrosine kinase axis regulates cellular plasticity and treatment response.Cellular signalling · 2026Article
- Integrative molecular analyses of lineage identity and morphology in aggressive variant prostate cancer.NPJ precision oncology · 2026Article
- Molecular decoupling of lineage identity and morphology in aggressive variant prostate cancer.medRxiv : the preprint server for health sciences · 2026Article
- Multi-omics analysis constructs a novel neuroendocrine prostate cancer classifier and classification system.Scientific reports · 2025Article
- Advances in tumor subclone formation and mechanisms of growth and invasion.Journal of translational medicine · 2025Review
- Harnessing nanotechnology for stem-cell therapies: revolutionizing neurodegenerative disorder treatments - a state-of-the-art update.Frontiers in pharmacology · 2025Review
- Comprehensive review of drug resistance in mammalian cancer stem cells: implications for cancer therapy.Cancer cell international · 2024Review
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
Abstract
To resist lineage-dependent therapies such as androgen receptor inhibition, prostate luminal epithelial adenocarcinoma cells often adopt a stem-like state resulting in lineage plasticity and phenotypic heterogeneity. Castrate-resistant prostate adenocarcinoma can transition to neuroendocrine (NE) and occasionally to amphicrine, co-expressed luminal and NE, phenotypes. We developed castrate-resistant prostate cancer (CRPC) patient-derived organoid models that preserve heterogeneity of the originating tumor, including an amphicrine model displaying a range of luminal and NE phenotypes. To gain biological insight and to identify potential treatment targets within heterogeneous tumor cell populations, we assessed the lineage hierarchy and molecular characteristics of various CRPC tumor subpopulations. Transcriptionally similar stem/progenitor (St/Pr) cells were identified for all lineage populations. Lineage tracing in amphicrine CRPC showed that heterogeneity originated from distinct subclones of infrequent St/Pr cells that produced mainly quiescent differentiated amphicrine progeny. By contrast, adenocarcinoma CRPC progeny originated from St/Pr cells and self-renewing differentiated luminal cells. Neuroendocrine prostate cancer (NEPC) was composed almost exclusively of self-renewing St/Pr cells. Amphicrine subpopulations were enriched for secretory luminal, mesenchymal, and enzalutamide treatment persistent signatures that characterize clinical progression. Finally, the amphicrine St/Pr subpopulation was specifically depleted with an AURKA inhibitor, which blocked tumor growth. These data illuminate distinct stem cell (SC) characteristics for subtype-specific CRPC in addition to demonstrating a context for targeting differentiation-competent prostate SCs.
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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.