ArticleBritish journal of cancer2014
The cAMP phosphodiesterase-4D7 (PDE4D7) is downregulated in androgen-independent prostate cancer cells and mediates proliferation by compartmentalising cAMP at the plasma membrane of VCaP prostate cancer cells.
Article in British journal of cancer, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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31 citing papers in PubMed, 47 citations in OpenAlex.
- Platelet-neutrophil cooperation in cancer: mechanisms of metastatic niche formation and implications for prognostic stratification and therapy.Cellular oncology (Dordrecht, Netherlands) · 2026Review
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Phosphodiesterase 7: a potential novel therapeutic target in ovarian cancer.Frontiers in pharmacology · 2025Article
- The multifaceted role of phosphodiesterase 4 in tumor: from tumorigenesis to immunotherapy.Frontiers in immunology · 2025Review
- Elevated PDE4C level serves as a candidate diagnostic biomarker and correlates with poor survival in thyroid carcinoma.Scientific reports · 2024Article
- cAMP-phosphodiesterase 4D7 (PDE4D7) forms a cAMP signalosome complex with DHX9 and is implicated in prostate cancer progression.Molecular oncology · 2024Article
- Revisiting the roles of cAMP signalling in the progression of prostate cancer.The Biochemical journal · 2023Article
- Reduced PDE4D7 in prostate cancer correlates with genomic downregulation within the upstream PDE4D coding region.Future science OA · 2023Article
- Loss of PDE4D7 expression promotes androgen independence, neuroendocrine differentiation and alterations in DNA repair: implications for therapeutic strategies.British journal of cancer · 2023Article
- Ablation of specific long PDE4D isoforms increases neurite elongation and conveys protection against amyloid-β pathology.Cellular and molecular life sciences : CMLS · 2023Article
- The CAPRA&PDE4D5/7/9 Prognostic Model Is Significantly Associated with Adverse Post-Surgical Pathology Outcomes.Cancers · 2022Article
- A cAMP signalosome in primary cilia drives gene expression and kidney cyst formation.EMBO reports · 2022Article
- The regulatory role of PDE4B in the progression of inflammatory function study.Frontiers in pharmacology · 2022Review
- PAN-selective inhibition of cAMP-phosphodiesterase 4 (PDE4) induces gastroparesis in mice.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020Article
- PDE4 subtypes in cancer.Oncogene · 2020Review
- Chorea-related mutations in PDE10A result in aberrant compartmentalization and functionality of the enzyme.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Understanding PDE4's function in Alzheimer's disease; a target for novel therapeutic approaches.Biochemical Society transactions · 2019Review
- Therapeutic targeting of 3',5'-cyclic nucleotide phosphodiesterases: inhibition and beyond.Nature reviews. Drug discovery · 2019Review
- Small-molecule allosteric activators of PDE4 long form cyclic AMP phosphodiesterases.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Targeting B-Raf inhibitor resistant melanoma with novel cell penetrating peptide disrupters of PDE8A - C-Raf.BMC cancer · 2019Article
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
backgroundIsoforms of the PDE4 family of cAMP-specific phosphodiesterases (PDEs) are expressed in a cell type-dependent manner and contribute to underpinning the paradigm of intracellular cAMP signal compartmentalisation. Here we identify the differential regulation of the PDE4D7 isoform during prostate cancer progression and uncover a role in controlling prostate cancer cell proliferation.
methodsPDE4 transcripts from 19 prostate cancer cell lines and xenografts were quantified by qPCR. PDE4D7 expression was further investigated because of its significant downregulation between androgen-sensitive (AS) and androgen-insensitive (AI) samples. Western blot analysis, PDE activity assay, immunofluorescent staining and cAMP responsive FRET assays were used to investigate the sub-plasma membrane localisation of a population of PDE4D7 in VCaP (AS) and PC3 (AI) cell lines. Disruption of this localisation pattern using dominant-negative protein expression and siRNA knockdown showed that PDE4D7 acts in opposition to proliferative signalling as assessed by electrical impedance-based proliferation assays.
resultsHere we identify the differential regulation of the PDE4D7 isoform during prostate cancer progression. PDE4D7 is highly expressed in AS cells and starkly downregulated in AI samples. The significance of this downregulation is underscored by our finding that PDE4D7 contributes a major fraction of cAMP degrading PDE activity tethered at the plasma membrane and that displacement of PDE4D7 from this compartment leads to an increase in the proliferation of prostate cancer cells. PDE4D7 mRNA expression is not, however, directly regulated by the androgen receptor signalling axis despite an overlapping genomic structure with the androgen responsive gene PART1. PDE4D7, which locates to the plasma membrane, acts to supress aberrant non-steroidal growth signals within the prostate or AS metastasis.
conclusionsPDE4D7 expression is significantly downregulated between AS and AI cell phenotypes. This change in expression potentially provides a novel androgen-independent biomarker and manipulation of its activity or its expression may provide therapeutic possibilities and insights into contributory aspects of the complex molecular pathology of prostate cancer.
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