ArticleCarcinogenesis2018
cAMP regulated EPAC1 supports microvascular density, angiogenic and metastatic properties in a model of triple negative breast cancer.
Article in Carcinogenesis, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- Uncovering Oncogenic Mechanisms of Tumor Suppressor Genes in Breast Cancer Multi-Omics Data.International journal of molecular sciences · 2022Pooled it
- The "Cold Tumor" to "Hot Tumor" transformation strategy for triple-negative breast cancer: from mechanism to clinical translation.Molecular and cellular biochemistry · 2026Review
- Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.Pharmacological reviews · 2025Review
- Mismatch repair-proficient tumor footprints in the sands of immune desert: mechanistic constraints and precision platforms.Frontiers in immunology · 2024Review
- 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
- Proteins Found in the Triple-Negative Breast Cancer Secretome and Their Therapeutic Potential.International journal of molecular sciences · 2023Review
- Microarray analysis of breast cancer gene expression profiling in response to 2-deoxyglucose, metformin, and glucose starvation.Cancer cell international · 2022Article
- Combinatorial delivery of CPI444 and vatalanib loaded on PEGylated graphene oxide as an effective nanoformulation to target glioblastoma multiforme:Frontiers in oncology · 2022Article
- INHBB is a novel prognostic biomarker and correlated with immune infiltrates in gastric cancer.Frontiers in genetics · 2022Article
- Intuitive repositioning of an anti-depressant drug in combination with tivozanib: precision medicine for breast cancer therapy.Molecular and cellular biochemistry · 2021Article
- Article
- Benefits of functional assays in personalized cancer medicine: more than just a proof-of-concept.Theranostics · 2021Review
- Visualization and bibliometric analysis of cAMP signaling system research trends and hotspots in cancer.Journal of Cancer · 2021Article
- Amalgamation of PI3K and EZH2 blockade synergistically regulates invasion and angiogenesis: combination therapy for glioblastoma multiforme.Oncotarget · 2020Article
- Bioengineered siRNA-Based Nanoplatforms Targeting Molecular Signaling Pathways for the Treatment of Triple Negative Breast Cancer: Preclinical and Clinical Advancements.Pharmaceutics · 2020Review
- Review: Role of cAMP signaling in diabetic retinopathy.Molecular vision · 2020Review
- POPDC3 is a potential biomarker for prognosis and radioresistance in patients with head and neck squamous cell carcinoma.Oncology letters · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Breast cancer is a leading cause of cancer-related mortality in women. Triple-negative breast cancer (TNBC; HER2-, ER-/PR-) is an aggressive subtype prone to drug resistance and metastasis, which is characterized by high intratumor microvascular density (iMVD) resulting from angiogenesis. However, the mechanisms contributing to the aggressive phenotypes of TNBC remain elusive. We recently reported that down-regulation of exchange factor directly activated by cyclic AMP (cAMP), also known as EPAC1, leads to a reduction in metastatic properties including proliferation and cell migration in TNBC cell lines. Here, we report that EPAC1 supports TNBC-induced angiogenesis, tumor cell migration and invasiveness as well as pro-metastatic phenotypes in endothelial cells induced through the tumor secretome. Using an approach that integrates proteomics with bioinformatics and gene ontologies, we elucidate that EPAC1 supports a tumor-secreted network of angiogenic, cell adhesion and cell migratory pathways. Using confocal microscopy, we show that signaling molecules involved in focal adhesion, including Paxillin and MENA, are down-regulated in the absence of EPAC1, and electric cell substrate impedance sensing technique confirmed a role for EPAC1 on TNBC-induced endothelial cell permeability. Finally, to provide a translational bridge, we studied iMVD and therapy response using a primary human tumor explant assay, CANscriptTM, which suggests a link between therapy-modulated neovascularization and drug sensitivity. These data provide mechanistic insight into the role of EPAC1 in regulating the tumor microenvironment, iMVD and cancer cell-induced angiogenesis, a dynamic mechanism under drug pressure that may associate to treatment failure.
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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.