ArticlePloS one2012
A novel interplay between Rap1 and PKA regulates induction of angiogenesis in prostate cancer.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 24 citations in OpenAlex.
- Oncolytic vaccinia virus encoding constitutively active EPAC remodels the tumor microenvironment to enhance therapeutic efficacy with chemotherapy and surgery.Journal for immunotherapy of cancer · 2026Article
- Downregulation of uncoupling protein 1 by hypermethylation in gastric cancer activatesWorld journal of gastrointestinal oncology · 2025Article
- Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.Pharmacological reviews · 2025Review
- Cordycepin Triphosphate as a Potential Modulator of Cellular Plasticity in Cancer via cAMP-Dependent Pathways: An In Silico Approach.International journal of molecular sciences · 2024Article
- Revisiting the roles of cAMP signalling in the progression of prostate cancer.The Biochemical journal · 2023Article
- Review
- Identification of phenotype-specific networks from paired gene expression-cell shape imaging data.Genome research · 2022Article
- Targeting Protein Kinases and Epigenetic Control as Combinatorial Therapy Options for Advanced Prostate Cancer Treatment.Pharmaceutics · 2022Review
- The Role of Neuropeptide-Stimulated cAMP-EPACs Signalling in Cancer Cells.Molecules (Basel, Switzerland) · 2022Review
- The Role of Epac in Cancer Progression.International journal of molecular sciences · 2020Review
- Identification of potential key genes in esophageal adenocarcinoma using bioinformatics.Experimental and therapeutic medicine · 2019Article
- Insights into exchange factor directly activated by cAMP (EPAC) as potential target for cancer treatment.Molecular and cellular biochemistry · 2018Review
- Vascular Endothelial Growth Factor-A Exerts Diverse Cellular Effects via Small G Proteins, Rho and Rap.International journal of molecular sciences · 2018Review
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- EPAC1 overexpression is a prognostic marker and its inhibition shows promising therapeutic potential for gastric cancer.Oncology reports · 2017Article
- Activation of P2X7 and P2Y11 purinergic receptors inhibits migration and normalizes tumor-derived endothelial cells via cAMP signaling.Scientific reports · 2016Article
- The pleiotropic role of exchange protein directly activated by cAMP 1 (EPAC1) in cancer: implications for therapeutic intervention.Acta biochimica et biophysica Sinica · 2016Review
- Pharmacological inhibition and genetic knockdown of exchange protein directly activated by cAMP 1 reduce pancreatic cancer metastasis in vivo.Molecular pharmacology · 2015Article
- PKA turnover by the REGγ-proteasome modulates FoxO1 cellular activity and VEGF-induced angiogenesis.Journal of molecular and cellular cardiology · 2014Article
- Protein kinase A-dependent phosphorylation of Rap1 regulates its membrane localization and cell migration.The Journal of biological chemistry · 2013Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Angiogenesis inhibition is an important therapeutic strategy for advanced stage prostate cancer. Previous work from our laboratory showed that sustained stimulation of Rap1 by 8-pCPT-2'-O-Me-cAMP (8CPT) via activation of Epac, a Rap1 GEF, or by expression of a constitutively active Rap1 mutant (cRap1) suppresses endothelial cell chemotaxis and subsequent angiogenesis. When we tested this model in the context of a prostate tumor xenograft, we found that 8CPT had no significant effect on prostate tumor growth alone. However, in cells harboring cRap1, 8CPT dramatically inhibited not only prostate tumor growth but also VEGF expression and angiogenesis within the tumor microenvironment. Subsequent analysis of the mechanism revealed that, in prostate tumor epithelial cells, 8CPT acted via stimulation of PKA rather than Epac/Rap1. PKA antagonizes Rap1 and hypoxic induction of 1α protein expression, VEGF production and, ultimately, angiogenesis. Together these findings provide evidence for a novel interplay between Rap1, Epac, and PKA that regulates tumor-stromal induction of angiogenesis.
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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.