ArticleOncogene2010
Regulation of the NRSF/REST gene by methylation and CREB affects the cellular phenotype of small-cell lung cancer.
Article in Oncogene, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 89 citations in OpenAlex.
- Proteome-wide identification of the druggable CRBN interactome.Nature biotechnology · 2026Article
- Proliferation of activated hepatic stellate cells requires REST.Molecular medicine (Cambridge, Mass.) · 2026Article
- The interplay between metabolism and neuroinflammation in epilepsy: mechanisms and therapeutic perspectives.Journal of neuroinflammation · 2025Review
- Loss of negative regulation by HDAC1 and REST contributes to MAD1 overexpression in breast cancer.Molecular biology of the cell · 2025Article
- Small intestinal neuroendocrine tumors lack early genomic drivers, acquire DNA repair defects and harbor hallmarks of low REST expression.Scientific reports · 2025Article
- REST Is Restless in Neuronal and Non-Neuronal Virus Infections: An In Silico Analysis-Based Perspective.Viruses · 2025Review
- Tudor-SN exacerbates pathological vascular remodeling by promoting the polyubiquitination of PTEN via NEDD4-1.Journal of biomedical science · 2024Article
- Overexpression of REST Represses the Epithelial-Mesenchymal Transition Process and Decreases the Aggressiveness of Prostate Cancer Cells.International journal of molecular sciences · 2024Article
- REST Is Not Resting: REST/NRSF in Health and Disease.Biomolecules · 2023Review
- DNA methylome analysis reveals potential alterations contributing to the progression of bronchial hyperplasia.Molecular biology reports · 2023Article
- ZNF133 is a potent suppressor in breast carcinogenesis through dampening L1CAM, a driver for tumor progression.Oncogene · 2023Article
- Cholinergic regulation of vascular endothelial function by human ChATProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Systematic analysis identifies REST as an oncogenic and immunological biomarker in glioma.Scientific reports · 2023Article
- The CRHR1/CREB/REST signaling cascade regulates mammalian embryonic neural stem cell properties.EMBO reports · 2023Article
- In-depth molecular analysis of combined and co-primary pulmonary large cell neuroendocrine carcinoma and adenocarcinoma.International journal of cancer · 2022Article
- A reassessment of Jackson's checklist and identification of two Down syndrome sub-phenotypes.Scientific reports · 2022Article
- βIII-Tubulin Gene Regulation in Health and Disease.Frontiers in cell and developmental biology · 2022Review
- RNA Splicing Factors SRRM3 and SRRM4 Distinguish Molecular Phenotypes of Castration-Resistant Neuroendocrine Prostate Cancer.Cancer research · 2021Article
- Neuroendocrine-Related Circulating Transcripts in Small-Cell Lung Cancers: Detection Methods and Future Perspectives.Cancers · 2021Review
- The Transcriptional Complex Sp1/KMT2A by Up-Regulating Restrictive Element 1 Silencing Transcription Factor Accelerates Methylmercury-Induced Cell Death in Motor Neuron-Like NSC34 Cells Overexpressing SOD1-G93A.Frontiers in neuroscience · 2021Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The neuron-restrictive silencer factor/RE1-silencing transcription factor (NRSF/REST) is a negative regulator of gene expression restricting the expression of neuronal genes to the nervous system. NRSF/REST is highly expressed in non-neuronal tissues like the lung. In previous work, we identified small-cell lung cancer (SCLC) cell lines with no detectable NRSF/REST expression that, as a consequence, expressed neuronal markers like L1-cell adhesion molecule (L1-CAM) and neural cell adhesion molecule (NCAM). The loss of NRSF/REST expression was linked to malignant progression; however, its mechanistic role remained elusive. Here, we show that NRSF/REST itself, rather than one of its regulated genes, acts like a classic tumour suppressor, being in part regulated by methylation. In SCLCs, NRSF/REST is positively regulated by CREB, with an NRSF/REST promoter fragment showing cell type specificity. Downstream, NRSF/REST directly regulates AKT2, in which NRSF/REST loss leads to an epidermal growth factor-mediated de-regulation of AKT-Serine473 phosphorylation, important for cellular proliferation and survival. Assaying anchorage-independent growth, we observed that with reduced NRSF/REST expression, proliferation was significantly enhanced, whereas NRSF/REST rescue decreased the potential of cells to grow anchorage independently. Our observations support the fact that NRSF/REST may act as an important modulator of malignant progression in SCLC.
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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.