ArticleThe Journal of biological chemistry2013
cAMP-response element-binding protein (CREB) and NF-κB transcription factors are activated during prolonged hypoxia and cooperatively regulate the induction of matrix metalloproteinase MMP1.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers, 1 of them a synthesis that pooled it.
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Who cites it
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 66 citations in OpenAlex.
- Biological mechanisms of atropine in myopia control (Review).Molecular medicine reports · 2026Pooled it
- P53 - a new player in the metabolic adaptation of colorectal carcinoma cells under hypoxia.BMC cancer · 2026Article
- Major pathophysiological changes in pulmonary disease provided a molecular insight based on deep learning approach.Scientific reports · 2025Article
- Decoding the impact of MMP1+ malignant subsets on tumor-immune interactions: insights from single-cell and spatial transcriptomics.Cell death discovery · 2025Article
- Fragile X messenger ribonucleoprotein 1 (FMRP) regulates glycolytic gene expression under chronic hypoxia in HCT116 cells.Scientific reports · 2025Article
- Intracranial Aneurysm Biomarkers: A Convergence of Genetics, Inflammation, Oxidative Stress, and the Extracellular Matrix.International journal of molecular sciences · 2025Review
- An Attention-Based Deep Neural Network Model to Detect Cis-Regulatory Elements at the Single-Cell Level From Multi-Omics Data.Genes to cells : devoted to molecular & cellular mechanisms · 2025Article
- cAMP-PKA/EPAC signaling and cancer: the interplay in tumor microenvironment.Journal of hematology & oncology · 2024Review
- Transcriptomic signatures of severe acute mountain sickness during rapid ascent to 4,300 m.Frontiers in physiology · 2024Article
- Myricetin attenuates hypoxia-induced inflammation in human adipocytes.Molecular biology reports · 2023Article
- Longitudinal dynamics of the tumor hypoxia response: From enzyme activity to biological phenotype.Science advances · 2023Review
- The Brain at High Altitude: From Molecular Signaling to Cognitive Performance.International journal of molecular sciences · 2023Review
- Pancreatic cancer cells upregulate LPAR4 in response to isolation stress to promote an ECM-enriched niche and support tumour initiation.Nature cell biology · 2023Article
- Large-scale mapping of positional changes of hypoxia-responsive genes upon activation.Molecular biology of the cell · 2022Article
- MicroRNA-204/CREB5 axis regulates vasculogenic mimicry in breast cancer cells.Cancer biomarkers : section A of Disease markers · 2022Article
- Immunosuppressive mesenchymal stem cells aggregates incorporating hydrogel microspheres promote an in vitro invasion of cancer cells.Regenerative therapy · 2021Article
- Marek's disease virus US3 protein kinase phosphorylates chicken HDAC 1 and 2 and regulates viral replication and pathogenesis.PLoS pathogens · 2021Article
- Collagen release by human hepatic stellate cells requires vitamin C and is efficiently blocked by hydroxylase inhibition.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Role of Marek's Disease Virus (MDV)-Encoded UJournal of virology · 2020Article
- Crosstalk between EP2 and PPARα Modulates Hypoxic Signaling and Myopia Development in Guinea Pigs.Investigative ophthalmology & visual science · 2020Article
Corrections and comments
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Authors and funding
1 author at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Responses to low levels of oxygen (hypoxia) are essential to maintain homeostasis. During the hypoxic response, gene expression is altered by various transcription factors. The transcription factor, hypoxia-inducible factor (HIF), plays a central role in the hypoxic response. The α subunit of HIF, which is actively degraded during normoxia, becomes stabilized during hypoxia, which leads to HIF activation. A microarray analysis of HeLa cells showed that expression of matrix metalloproteinase 1 (MMP1) was markedly induced during prolonged hypoxia. CREB and NF-κB binding sites were identified in the MMP1 promoter region between 1945 and 1896 nucleotides upstream of the transcription start site. Assays with luciferase reporters demonstrated that HIF activity was induced during the early phase of hypoxia, whereas CREB and NF-κB were activated during the later (prolonged) phase. Depletion of CREB and/or NF-κB reduced MMP1 induction during prolonged hypoxia both at the mRNA and protein levels. A chromatin immunoprecipitation assay demonstrated binding of CREB and NF-κB to the MMP1 promoter. Finally, cell migration and invasion on a collagen matrix and pulmonary metastasis in nude mice were inhibited after depletion of CREB and NF-κB in MDA-MB-231 cells. Taken together, these results suggest that the cooperative action of CREB and NF-κB plays an important role to induce MMP1 expression during prolonged hypoxia and regulates cell migration and invasion in cancer cells.
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