ArticleMolecular and cellular biochemistry2017
Role of exchange protein directly activated by cAMP (EPAC1) in breast cancer cell migration and apoptosis.
Article in Molecular and cellular biochemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 57 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
- In vitro screening of the open-access Pandemic Response Box reveals ESI-09 as a compound with activity against Echinococcus multilocularis.International journal for parasitology. Drugs and drug resistance · 2025Article
- Transcriptomic analysis identifies enrichment of cAMP/PKA/CREB signaling in invasive lobular breast cancer.Breast cancer research : BCR · 2024Article
- Biochemical pharmacology of adenylyl cyclases in cancer.Biochemical pharmacology · 2024Review
- Acute myeloid leukemia with a novelLeukemia research reports · 2024Article
- The dual and multifaceted role of relaxin-2 in cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Review
- Article
- Exosomal hsa-let-7g-3p and hsa-miR-10395-3p derived from peritoneal lavage predict peritoneal metastasis and the efficacy of neoadjuvant intraperitoneal and systemic chemotherapy in patients with gastric cancer.Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association · 2023Article
- Evaluation ofAdvanced biomedical research · 2023Article
- EPAC Regulates Melanoma Growth by Stimulating mTORC1 Signaling and Loss of EPAC Signaling Dependence Correlates with Melanoma Progression.Molecular cancer research : MCR · 2022Article
- Review
- The Role of Neuropeptide-Stimulated cAMP-EPACs Signalling in Cancer Cells.Molecules (Basel, Switzerland) · 2022Review
- Epac: A Promising Therapeutic Target for Vascular Diseases: A Review.Frontiers in pharmacology · 2022Review
- AKAP9 Upregulation Predicts Unfavorable Prognosis in Pediatric Acute Myeloid Leukemia and Promotes Stemness Properties via the Wnt/β-Catenin Pathway.Cancer management and research · 2022Article
- Intuitive repositioning of an anti-depressant drug in combination with tivozanib: precision medicine for breast cancer therapy.Molecular and cellular biochemistry · 2021Article
- α1 adrenergic receptors in serum and saliva of patients with oral squamous cell carcinoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2021Article
- The Consequences of Soluble Epoxide Hydrolase Deletion on Tumorigenesis and Metastasis in a Mouse Model of Breast Cancer.International journal of molecular sciences · 2021Article
- Broad Impact of Exchange Protein Directly Activated by cAMP 2 (EPAC2) on Respiratory Viral Infections.Viruses · 2021Article
- The Orai1-AC8 Interplay: How Breast Cancer Cells Escape from Orai1 Channel Inactivation.Cells · 2021Review
- Subcellular Organization of the cAMP Signaling Pathway.Pharmacological reviews · 2021Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the current progress in cancer research and therapy, breast cancer remains the leading cause of mortality among half a million women worldwide. Migration and invasion of cancer cells are associated with prevalent tumor metastasis as well as high mortality. Extensive studies have powerfully established the role of prototypic second messenger cAMP and its two ubiquitously expressed intracellular cAMP receptors namely the classic protein kinaseA/cAMP-dependent protein kinase (PKA) and the more recently discovered exchange protein directly activated by cAMP/cAMP-regulated guanine nucleotide exchange factor (EPAC/cAMP-GEF) in cell migration, cell cycle regulation, and cell death. Herein, we performed the analysis of the Cancer Genome Atlas (TCGA) dataset to evaluate the essential role of cAMP molecular network in breast cancer. We report that EPAC1, PKA, and AKAP9 along with other molecular partners are amplified in breast cancer patients, indicating the importance of this signaling network. To evaluate the functional role of few of these proteins, we used pharmacological modulators and analyzed their effect on cell migration and cell death in breast cancer cells. Hence, we report that inhibition of EPAC1 activity using pharmacological modulators leads to inhibition of cell migration and induces cell death. Additionally, we also observed that the inhibition of EPAC1 resulted in disruption of its association with the microtubule cytoskeleton and delocalization of AKAP9 from the centrosome as analyzed by in vitro imaging. Finally, this study suggests for the first time the mechanistic insights of mode of action of a primary cAMP-dependent sensor, Exchange protein activated by cAMP 1 (EPAC1), via its interaction with A-kinase anchoring protein 9 (AKAP9). This study provides a new cell signaling cAMP-EPAC1-AKAP9 direction to the development of additional biotherapeutics for breast cancer.
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