ArticleOncogene2017
PDE4D promotes FAK-mediated cell invasion in BRAF-mutated melanoma.
Article in Oncogene, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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Who cites it
23 citing papers in PubMed, 41 citations in OpenAlex.
- Regulation of cAMP levels in osteocytes by mechano-sensitive focal adhesion kinase and phosphodiesterase 8A.iScience · 2026Article
- KTX207-mediated PDE4D degradation disrupts tumour cell migration, invasion, and angiogenic potential.Cell communication and signaling : CCS · 2026Article
- Crucial role of telomere maintenance-related genes in survival prediction and subtype identification in colorectal cancer.Frontiers in molecular biosciences · 2026Article
- Melanoma: Pathogenesis and Targeted Therapy.MedComm · 2026Review
- Nanodomain cAMP signaling in cardiac pathophysiology: potential for developing targeted therapeutic interventions.Physiological reviews · 2025Review
- PDE4D drives rewiring of the MAPK pathway in BRAF-mutated melanoma resistant to MAPK inhibitors.Cell communication and signaling : CCS · 2024Article
- Single-cell hdWGCNA reveals metastatic protective macrophages and development of deep learning model in uveal melanoma.Journal of translational medicine · 2024Article
- Characterization of the microenvironment in different immune-metabolism subtypes of cervical cancer with prognostic significance.Frontiers in genetics · 2023Article
- Is Apremilast a Safe Option in Patients with History of Melanoma? A Case Series and a Review of the Literature.The Journal of clinical and aesthetic dermatology · 2022Article
- Inhibition of PDE4 by apremilast attenuates skin fibrosis through directly suppressing activation of M1 and T cells.Acta pharmacologica Sinica · 2022Article
- Review
- Integrative QTL mapping and selection signatures in Groningen White Headed cattle inferred from whole-genome sequences.PloS one · 2022Article
- Transcriptional co-activator regulates melanocyte differentiation and oncogenesis by integrating cAMP and MAPK/ERK pathways.Cell reports · 2021Article
- Phosphodiesterase 4D Depletion/Inhibition Exerts Anti-Oncogenic Properties in Hepatocellular Carcinoma.Cancers · 2021Article
- Whole-genome screen identifies diverse pathways that negatively regulate ciliogenesis.Molecular biology of the cell · 2021Article
- Cyclic adenosine monophosphate (cAMP) signaling in melanocyte pigmentation and melanomagenesis.Pigment cell & melanoma research · 2021Review
- PDE4 subtypes in cancer.Oncogene · 2020Review
- Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond.Nature reviews. Drug discovery · 2019Review
- Inhibition of phosphodiesterase 4D decreases the malignant properties of DLD-1 colorectal cancer cells by repressing the AKT/mTOR/Myc signaling pathway.Oncology letters · 2019Article
- High expression of PDE4D correlates with poor prognosis and clinical progression in pancreaticductal adenocarcinoma.Journal of Cancer · 2019Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The cyclic AMP (cAMP) signaling pathway is critical in melanocyte biology for regulating differentiation. It is downregulated by phosphodiesterase (PDE) enzymes, which degrade cAMP itself. In melanoma evidence suggests that inhibition of the cAMP pathway by PDE type 4 (PDE4) favors tumor progression. For example, in melanomas harboring RAS mutations, the overexpression of PDE4 is crucial for MAPK pathway activation and proliferation induced by oncogenic RAS. Here we showed that PDE4D is overexpressed in BRAF-mutated melanoma cell lines, constitutively disrupting the cAMP pathway activation. PDE4D promoted melanoma invasion by interacting with focal adhesion kinase (FAK) through the scaffolding protein RACK1. Inhibition of PDE4 activity or inhibition of PDE4D interaction with FAK reduced invasion. PDE4D expression is increased in patients with advanced melanoma and PDE4D-FAK interaction is detectable in situ in metastatic melanoma. Our study establishes the role of PDE4D in BRAF-mutated melanoma as regulator of cell invasion, and suggests its potential as a target for preventing metastatic dissemination.
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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.