ArticleMolecular cancer2014
The role of high cell density in the promotion of neuroendocrine transdifferentiation of prostate cancer cells.
Article in Molecular cancer, 2014. 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, 29 citations in OpenAlex.
- Castration-resistant prostate cancer monitoring by cell-free circulating biomarkers.Frontiers in oncology · 2024Review
- Revisiting the roles of cAMP signalling in the progression of prostate cancer.The Biochemical journal · 2023Article
- Quantitative diffusion MRI in prostate cancer: Image quality, what we can measure and how it improves clinical assessment.European journal of radiology · 2023Review
- Variability of fluorescence intensity distribution measured by flow cytometry is influenced by cell size and cell cycle progression.Scientific reports · 2023Article
- Focus on the tumor microenvironment: A seedbed for neuroendocrine prostateFrontiers in cell and developmental biology · 2022Review
- Regulation of Neuroendocrine-like Differentiation in Prostate Cancer by Non-Coding RNAs.Non-coding RNA · 2021Review
- SLX4IP Promotes Telomere Maintenance in Androgen Receptor-Independent Castration-Resistant Prostate Cancer through ALT-like Telomeric PML Localization.Molecular cancer research : MCR · 2021Article
- Article
- The Role of lncRNAs TAPIR-1 and -2 as Diagnostic Markers and Potential Therapeutic Targets in Prostate Cancer.Cancers · 2020Article
- TRAIL-induced variation of cell signaling states provides nonheritable resistance to apoptosis.Life science alliance · 2019Article
- Targeting Wnt/EZH2/microRNA-708 signaling pathway inhibits neuroendocrine differentiation in prostate cancer.Cell death discovery · 2019Article
- Effect of A549 neuroendocrine differentiation on cytotoxic immune response.Endocrine connections · 2018Article
- Diffusion-weighted endorectal MR imaging at 3T for prostate cancer: correlation with tumor cell density and percentage Gleason pattern on whole mount pathology.Abdominal radiology (New York) · 2017Article
- Neuroendocrine differentiation in prostate cancer: key epigenetic players.Translational cancer research · 2017Article
- Article
- Opposite regulation of MDM2 and MDMX expression in acquisition of mesenchymal phenotype in benign and cancer cells.Oncotarget · 2015Article
- Quantitative measurement of cancer tissue biomarkers in the lab and in the clinic.Laboratory investigation; a journal of technical methods and pathology · 2015Review
- Prostate cancer and neuroendocrine differentiation: more neuronal, less endocrine?Frontiers in oncology · 2015Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTumor heterogeneity and the plasticity of cancer cells present challenges for effective clinical diagnosis and therapy. Such challenges are epitomized by neuroendocrine transdifferentiation (NED) and the emergence of neuroendocrine-like cancer cells in prostate tumors. This phenomenon frequently arises from androgen-depleted prostate adenocarcinoma and is associated with the development of castration-resistant prostate cancer and poor prognosis.
resultsIn this study, we showed that NED was evoked in both androgen receptor (AR)-positive and AR-negative prostate epithelial cell lines by growing the cells to a high density. Androgen depletion and high-density cultivation were both associated with cell cycle arrest and deregulated expression of several cell cycle regulators, such as p27Kip1, members of the cyclin D protein family, and Cdk2. Dual inhibition of Cdk1 and Cdk2 using pharmacological inhibitor or RNAi led to modulation of the cell cycle and promotion of NED. We further demonstrated that the cyclic adenosine 3', 5'-monophosphate (cAMP)-mediated pathway is activated in the high-density conditions. Importantly, inhibition of cAMP signaling using a specific inhibitor of adenylate cyclase, MDL-12330A, abolished the promotion of NED by high cell density.
conclusionsTaken together, our results imply a new relationship between cell cycle attenuation and promotion of NED and suggest high cell density as a trigger for cAMP signaling that can mediate reversible NED in prostate cancer cells.
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