ArticleCancers2019
Phosphodiesterase 5 (PDE5) Is Highly Expressed in Cancer-Associated Fibroblasts and Enhances Breast Tumor Progression.
Article in Cancers, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- Assessing the impact of phosphodiesterase 5 inhibitors on survival in men after treatment for rectal cancer.Frontiers in oncology · 2026Article
- Integration of cAMP and TRPV4 Signaling to Optimize Collagen Remodeling for Management of Fibrosis.Cells · 2025Review
- Repurposing of phosphodiesterase-5 inhibitor sildenafil as a therapeutic agent to prevent gastric cancer growth through suppressing c-MYC stability for IL-6 transcription.Communications biology · 2025Article
- A novel phosphodiesterase target as a therapeutic approach: inhibiting DEN-induced hepatocellular carcinoma progression.EXCLI journal · 2025Review
- Sodium arsenite-induced DNA methylation alterations exacerbated by p53 knockout in MCF7 cells.Heliyon · 2024Article
- Evidence that CRISPR-Cas9 Y537S-mutant expressing breast cancer cells activate Yes-associated protein 1 to driving the conversion of normal fibroblasts into cancer-associated fibroblasts.Cell communication and signaling : CCS · 2024Article
- The Emerging Role of Phosphodiesterase 5 Inhibition in Neurological Disorders: The State of the Art.Cells · 2024Review
- Integrating computational and experimental chemical biology revealed variable anticancer activities of phosphodiesterase isoenzyme 5 inhibitors (PDE5i) in lung cancer.RSC medicinal chemistry · 2024Article
- Potential drug targets for tumors identified through Mendelian randomization analysis.Scientific reports · 2024Article
- STGIC: A graph and image convolution-based method for spatial transcriptomic clustering.PLoS computational biology · 2024Article
- Combination Therapy as a Promising Way to Fight Oral Cancer.Pharmaceutics · 2023Review
- Article
- The role of cancer-associated fibroblasts in breast cancer metastasis.Frontiers in oncology · 2023Review
- Phosphodiesterase type 5 inhibitors enhance chemotherapy in preclinical models of esophageal adenocarcinoma by targeting cancer-associated fibroblasts.Cell reports. Medicine · 2022Article
- Overcoming Therapy Resistance and Relapse in TNBC: Emerging Technologies to Target Breast Cancer-Associated Fibroblasts.Biomedicines · 2021Review
- Discovery of catalytic-site-fluorescent probes for tracing phosphodiesterase 5 in living cells.RSC advances · 2021Article
- Cancer-associated fibroblasts: overview, progress, challenges, and directions.Cancer gene therapy · 2021Review
- On the Viability of Tadalafil-BasedACS omega · 2021Article
- Review
- New Approaches in Oncology for Repositioning Drugs: The Case of PDE5 Inhibitor Sildenafil.Frontiers in oncology · 2021Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
The overexpression of phosphodiesterase (PDE) 5 is frequently found in various human cancers, such as those of the breast. However, PDE5's role in the tumor microenvironment is still unknown. As PDE5 represents a high-value therapeutic target, we investigated whether the expression and function of PDE5 in breast cancer-associated fibroblasts (CAFs) may be clinically relevant to malignant progression. PDE5 expression was increased in human breast cancer stroma compared with normal stroma and was correlated to a shorter overall survival. Treatment of CAFs, isolated from breast tumor biopsies, with selective PDE5 inhibitors inhibited their proliferation, motility, and invasiveness, and negatively controlled tumor-stroma interactions in both 'in vitro' and 'in vivo' models. PDE5 stable overexpression transformed immortalized mouse embryonic fibroblasts (MEFs) towards an activated fibroblast phenotype, impacting their intrinsic characteristics and paracrine effects on breast cancer cell growth and migration through an enhanced production of the C-X-C motif chemokine 16 (CXCL16). On the other hand, CAF exposure to PDE5 inhibitors was associated with reduced CXCL16 expression and secretion. Importantly, CXCL16 levels in breast cancer stroma showed a strong correlation with PDE5 levels and poor patient outcomes. In conclusion, PDE5 is overexpressed in breast cancer stroma, enhances the tumor-stimulatory activities of fibroblasts, and impacts clinical outcomes; thus, we propose this enzyme as an attractive candidate for prognosis and a potential target for treatments in breast cancer patients.
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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.