ArticleOncotarget2017
Phosphodiesterase 10A is overexpressed in lung tumor cells and inhibitors selectively suppress growth by blocking β-catenin and MAPK signaling.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 47 citations in OpenAlex.
- Developing a Phosphodiesterase 10A Inhibitor as a Novel Therapeutic Agent for Triple-Negative Breast Cancer.Cells · 2026Article
- ADT-030, a novel PDE10 inhibitor, demonstrates potent antitumor activity in pancreatic ductal adenocarcinoma.bioRxiv : the preprint server for biology · 2026Article
- NSAID-encapsulated nanoparticles as a targeted therapeutic platform for modulating chronic inflammation and inhibiting cancer progression: a review.Inflammopharmacology · 2025Review
- Cyclic nucleotide phosphodiesterases as drug targets.Pharmacological reviews · 2025Review
- Inhalable Carbonyl Sulfide Donor-Hybridized Selective Phosphodiesterase 10A Inhibitor for Treating Idiopathic Pulmonary Fibrosis by Inhibiting Tumor Growth Factor-β Signaling and Activating the cAMP/Protein Kinase A/cAMP Response Element-Binding Protein (CREB)/p53 Axis.ACS pharmacology & translational science · 2025Article
- Novel Celecoxib Derivative, RF26, Blocks Colon Cancer Cell Growth by Inhibiting PDE5, Activating cGMP/PKG Signaling, and Suppressing β-catenin-dependent Transcription.Anti-cancer agents in medicinal chemistry · 2025Article
- PDE10A as a novel diagnostic and therapeutic target in cancer: insights and challenges.Frontiers in oncology · 2025Review
- Network Pharmacology and Molecular Docking Study on the Mechanism of the Therapeutic Effect of Strychni Semen in NSCLC.Biological procedures online · 2024Article
- Sodium arsenite-induced DNA methylation alterations exacerbated by p53 knockout in MCF7 cells.Heliyon · 2024Article
- Phosphodiesterase Inhibition to Sensitize Non-Small-Cell Lung Cancer to Pemetrexed: A Double-Edged Strategy.Cancers · 2024Article
- PDE10A Inactivation Prevents Doxorubicin-Induced Cardiotoxicity and Tumor Growth.Circulation research · 2023Article
- Genomic Loss and Epigenetic Silencing of the FOSL1 Tumor Suppressor Gene in Radiation-induced Neoplastic Transformation of Human CGL1 Cells Alters the Tumorigenic Phenotype In Vitro and In Vivo.Radiation research · 2023Article
- Phosphodiesterase type 10A inhibitor attenuates lung fibrosis by targeting myofibroblast activation.iScience · 2023Article
- Once upon a Testis: The Tale of Cyclic Nucleotide Phosphodiesterase in Testicular Cancers.International journal of molecular sciences · 2023Review
- Article
- Landscape and clinical impact of metabolic alterations in non-squamous non-small cell lung cancer.Translational lung cancer research · 2022Article
- Phosphodiesterase 10A (PDE10A) as a novel target to suppress β-catenin and RAS signaling in epithelial ovarian cancer.Journal of ovarian research · 2022Article
- Role of PDE10A in vascular smooth muscle cell hyperplasia and pathological vascular remodelling.Cardiovascular research · 2022Article
- NSAIDs and Cancer Resolution: New Paradigms beyond Cyclooxygenase.International journal of molecular sciences · 2022Review
- cAMP-specific phosphodiesterase 8A and 8B isoforms are differentially expressed in human testis and Leydig cell tumor.Frontiers in endocrinology · 2022Article
Corrections and comments
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Authors and funding
19 authors at 3 institutions in 1 country.
Funding
Abstract
Phosphodiesterase 10A (PDE10) is a cyclic nucleotide (e.g. cGMP) degrading enzyme highly expressed in the brain striatum where it plays an important role in dopaminergic neurotransmission, but has limited expression and no known physiological function outside the central nervous system. Here we report that PDE10 mRNA and protein levels are strongly elevated in human non-small cell lung cancer cells and lung tumors compared with normal human airway epithelial cells and lung tissue, respectively. Genetic silencing of PDE10 or inhibition by small molecules such as PQ10 was found to selectively inhibit the growth and colony formation of lung tumor cells. PQ10 treatment of lung tumor cells rapidly increased intracellular cGMP levels and activated cGMP-dependent protein kinase (PKG) at concentrations that inhibit lung tumor cell growth. PQ10 also increased the phosphorylation of β-catenin and reduced its levels, which paralleled the suppression of cyclin D1 and survivin but preceded the activation of PARP and caspase cleavage. PQ10 also suppressed RAS-activated RAF/MAPK signaling within the same concentration range and treatment period as required for cGMP elevation and PKG activation. These results show that PDE10 is overexpressed during lung cancer development and essential for lung tumor cell growth in which inhibitors can selectively induce apoptosis by increasing intracellular cGMP levels and activating PKG to suppress oncogenic β-catenin and MAPK signaling.
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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.