ArticleMolecular cancer research : MCR2012
Notch signaling modulates hypoxia-induced neuroendocrine differentiation of human prostate cancer cells.
Article in Molecular cancer research : MCR, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
46 citing papers in PubMed, 87 citations in OpenAlex.
- Effects of genistein supplementation on genome‑wide DNA methylation and gene expression in patients with localized prostate cancer.International journal of oncology · 2017Trial
- Lineage plasticity and histological transformation: tumor histology as a spectrum.Cell research · 2025Review
- Widespread activation and critical role of EMT and stemness in the neuroendocrine differentiation of prostate cancer (Review).Oncology reports · 2025Review
- CXCR4-LASP1-G9a-SNAIL axis drives NEPC transdifferentiation via induction of EMT and downregulation of REST.Cell genomics · 2025Article
- A novel role for Neurog2 in MYCN driven neuroendocrine plasticity of prostate cancer.Oncogene · 2025Article
- ETV5 reduces androgen receptor expression and induces neural stem-like properties during neuroendocrine prostate cancer development.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Regulation of Molecular Biomarkers Associated with the Progression of Prostate Cancer.International journal of molecular sciences · 2024Review
- Article
- The roles of proteases in prostate cancer.IUBMB life · 2023Review
- Advances in neuroendocrine prostate cancer research: From model construction to molecular network analyses.Laboratory investigation; a journal of technical methods and pathology · 2022Review
- Article
- RB1 loss in castration-resistant prostate cancer confers vulnerability to LSD1 inhibition.Oncogene · 2022Article
- βIII-Tubulin Gene Regulation in Health and Disease.Frontiers in cell and developmental biology · 2022Review
- Castration-Induced Downregulation of SPARC in Stromal Cells Drives Neuroendocrine Differentiation of Prostate Cancer.Cancer research · 2021Article
- N-cadherin inhibitor creates a microenvironment that protect TILs from immune checkpoints and Treg cells.Journal for immunotherapy of cancer · 2021Article
- hASH1 nuclear localization persists in neuroendocrine transdifferentiated prostate cancer cells, even upon reintroduction of androgen.Scientific reports · 2019Article
- Multiplex profiling identifies clinically relevant signalling proteins in an isogenic prostate cancer model of radioresistance.Scientific reports · 2019Article
- Neuroendocrine Differentiation of Prostate Cancer-An Intriguing Example of Tumor Evolution at Play.Cancers · 2019Review
- Updates on the Role of Molecular Alterations and NOTCH Signalling in the Development of Neuroendocrine Neoplasms.Journal of clinical medicine · 2019Review
- Neuroendocrine Differentiation in Prostate Cancer: Emerging Biology, Models, and Therapies.Cold Spring Harbor perspectives in medicine · 2019Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
unlabelledProstate carcinoma is among the most common causes of cancer-related death in men, representing 15% of all male malignancies in developed countries. Neuroendocrine differentiation (NED) has been associated with tumor progression, poor prognosis, and with the androgen-independent status. Currently, no successful therapy exists for advanced, castration-resistant disease. Because hypoxia has been linked to prostate cancer progression and unfavorable outcome, we sought to determine whether hypoxia would impact the degree of neuroendocrine differentiation of prostate cancer cells in vitro.
resultsExposure of LNCaP cells to low oxygen tension induced a neuroendocrine phenotype, associated with an increased expression of the transcription factor neurogenin3 and neuroendocrine markers, such as neuron-specific enolase, chromogranin A, and β3-tubulin. Moreover, hypoxia triggered a significant decrease of Notch 1 and Notch 2 mRNA and protein expression, with subsequent downregulation of Notch-mediated signaling, as shown by reduced levels of the Notch target genes, Hes1 and Hey1. NED was promoted by attenuation of Hes1 transcription, as cells expressing a dominant-negative form of Hes1 displayed increased levels of neuroendocrine markers under normoxic conditions. Although hypoxia downregulated Notch 1 and Notch 2 mRNA transcription and receptor activation also in the androgen-independent cell lines, PC-3 and Du145, it did not change the extent of NED in these cultures, suggesting that androgen sensitivity may be required for transdifferentiation to occur.
conclusionsHypoxia induces NED of LNCaP cells in vitro, which seems to be driven by the inhibition of Notch signaling with subsequent downregulation of Hes1 transcription.
Indexed as
Identifiers
What OpenQuestion 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 OpenQuestion graph.