ArticleExperimental cell research2011
The Raf/MEK/extracellular signal-regulated kinase 1/2 pathway can mediate growth inhibitory and differentiation signaling via androgen receptor downregulation in prostate cancer cells.
Article in Experimental cell research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 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
32 citing papers in PubMed, 45 citations in OpenAlex.
- ERKed by too much signaling: from oncogenic driver to therapeutic vulnerability.Cellular and molecular life sciences : CMLS · 2026Review
- Regulation of Molecular Biomarkers Associated with the Progression of Prostate Cancer.International journal of molecular sciences · 2024Review
- ERK pathway agonism for cancer therapy: evidence, insights, and a target discovery framework.NPJ precision oncology · 2024Review
- Prostate Cancer Stem Cells: Biology and Treatment Implications.International journal of molecular sciences · 2023Review
- DUSP4 protects BRAF- and NRAS-mutant melanoma from oncogene overdose through modulation of MITF.Life science alliance · 2022Article
- A Review of the Pathophysiological Mechanisms Underlying Castration-resistant Prostate Cancer.Research and reports in urology · 2021Review
- Phosphoinositide-dependent Kinase-1 (PDPK1) regulates serum/glucocorticoid-regulated Kinase 3 (SGK3) for prostate cancer cell survival.Journal of cellular and molecular medicine · 2020Article
- Mortalin (HSPA9) facilitatesScience signaling · 2020Article
- Prostate tumor neuroendocrine differentiation via EMT: The road less traveled.Asian journal of urology · 2019Review
- Systemic surfaceome profiling identifies target antigens for immune-based therapy in subtypes of advanced prostate cancer.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Article
- A cellular threshold for active ERK1/2 levels determines Raf/MEK/ERK-mediated growth arrest versus death responses.Cellular signalling · 2018Article
- Article
- Catfish rhamnose-binding lectin induces GGlycoconjugate journal · 2017Article
- ERK1/2 can feedback-regulate cellular MEK1/2 levels.Cellular signalling · 2015Article
- Active ERK2 is sufficient to mediate growth arrest and differentiation signaling.The FEBS journal · 2015Article
- Loss of Dlg5 expression promotes the migration and invasion of prostate cancer cells via Girdin phosphorylation.Oncogene · 2015Article
- Prostate cancer stem cells: deciphering the origins and pathways involved in prostate tumorigenesis and aggression.Oncotarget · 2015Review
- Novel combination of docetaxel and thymoquinone induces synergistic cytotoxicity and apoptosis in DU-145 human prostate cancer cells by modulating PI3K-AKT pathway.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2015Article
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Upregulated ERK1/2 activity is correlated with androgen receptor (AR) downregulation in certain prostate cancer (PCa) that exhibits androgen deprivation-induced neuroendocrine differentiation, but its functional relevance requires elucidation. We found that sustained ERK1/2 activation using active Raf or MEK1/2 mutants is sufficient to induce AR downregulation at mRNA and protein levels in LNCaP. Downregulation of AR protein, but not mRNA, was blocked by proteasome inhibitors, MG132 and bortezomib, indicating that the pathway regulation is mediated at multiple points. Ectopic expression of a constitutively active AR inhibited Raf/MEK/ERK-mediated regulation of the differentiation markers, neuron-specific enolase and neutral endopeptidase, and the cyclin-dependent kinase inhibitors, p16(INK4A) and p21(CIP1), but not Rb phosphorylation and E2F1 expression, indicating that AR has a specific role in the pathway-mediated differentiation and growth inhibitory signaling. However, despite the sufficient role of Raf/MEK/ERK, its inhibition using U0126 or ERK1/2 knockdown could not block androgen deprivation-induced AR downregulation in an LNCaP neuroendocrine differentiation model, suggesting that additional signaling pathways are involved in the regulation. We additionally report that sustained Raf/MEK/ERK activity can downregulate full length as well as hormone binding domain-deficient AR isoforms in androgen-refractory C4-2 and CWR22Rv1, but not in LAPC4 and MDA-PCa-2b. Our study demonstrates a novel role of the Raf/MEK/ERK pathway in regulating AR expression in certain PCa types and provides an insight into PCa responses to its aberrant activation.
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.