ArticleExperimental & molecular medicine2016
Isoproterenol increases histone deacetylase 6 expression and cell migration by inhibiting ERK signaling via PKA and Epac pathways in human lung cancer cells.
Article in Experimental & molecular medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 28 citations in OpenAlex.
- Chronic βThe Journal of physiology · 2018Trial
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- Rap1-Dependent pathways in depression: Genetic, Epigenetic, and neuroinflammatory mechanisms shaping synaptic resilience.Molecular biology reports · 2025Review
- Alpha-melanocyte stimulating hormone (α-MSH): biology, clinical relevance and implication in melanoma.Journal of translational medicine · 2023Review
- Norepinephrine, beyond the Synapse: Coordinating Epigenetic Codes for Memory.International journal of molecular sciences · 2022Review
- Review
- Uveal Melanoma Cell Line Proliferation Is Inhibited by Ricolinostat, a Histone Deacetylase Inhibitor.Cancers · 2022Article
- Article
- The Role of Neuropeptide-Stimulated cAMP-EPACs Signalling in Cancer Cells.Molecules (Basel, Switzerland) · 2022Review
- Epac: A Promising Therapeutic Target for Vascular Diseases: A Review.Frontiers in pharmacology · 2022Review
- Emerging therapies for autosomal dominant polycystic kidney disease with a focus on cAMP signaling.Frontiers in molecular biosciences · 2022Review
- The Potentially Therapeutic Role of EPAC in Curbing the Process of Idiopathic Pulmonary Fibrosis via Differential Cellular Pathways.Journal of inflammation research · 2021Article
- The Role of Epac in Cancer Progression.International journal of molecular sciences · 2020Review
- The road to ERK activation: Do neurons take alternate routes?Cellular signalling · 2020Review
- Review
- A perspective profile of ADCY1 in cAMP signaling with drug-resistance in lung cancer.Journal of Cancer · 2019Review
- LncRNAs NR-026690 and ENST00000447867 are upregulated in CD4International journal of chronic obstructive pulmonary disease · 2019Article
- Overexpression of HDAC6 suppresses tumor cell proliferation and metastasis by inhibition of the canonical Wnt/β-catenin signaling pathway in hepatocellular carcinoma.Oncology letters · 2018Article
- Insights into exchange factor directly activated by cAMP (EPAC) as potential target for cancer treatment.Molecular and cellular biochemistry · 2018Review
- High expression of Ras-related protein 1A promotes an aggressive phenotype in colorectal cancer via PTEN/FOXO3/CCND1 pathway.Journal of experimental & clinical cancer research : CR · 2018Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Stress conditions are correlated with tumor growth, progression and metastasis. We hypothesized that stress signals might affect tumor progression via epigenetic control of gene expression and investigated the effects of stress signals on the expression levels of histone deacetylases (HDACs) and the underlying mechanisms of these effects in lung cancer cells. Treatment with isoproterenol (ISO), an analog of the stress signal epinephrine, increased the expression of HDAC6 protein and mRNA in H1299 lung cancer cells. ISO caused the deacetylation of α-tubulin and stimulated cell migration in an HDAC6-dependent manner. HDAC6 expression was increased by treatment with selective activators of cAMP-dependent protein kinase (PKA) or exchange protein activated by cAMP (Epac). ISO activated Rap1 via Epac, and constitutively active Rap1A increased the HDAC6 level; however, the knockdown of Rap1A decreased the 8-(4-cholorophenylthio)-2'-O-methyl-cAMP-induced increase in HDAC6 expression. Both PKA and Rap1A decreased c-Raf activation to inhibit extracellular signal-regulated kinase (ERK) signaling. Inhibition of ERK caused an increase in HDAC6 expression, and constitutively active MEK1 decreased the ISO-induced HDAC6 expression. We concluded that ISO increases HDAC6 expression via a PKA/Epac/ERK-dependent pathway that stimulates the migration of lung cancer cells. This study suggests that stress signals can stimulate the migration of cancer cells by inducing HDAC6 expression in lung cancer cells.
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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.