ArticleJournal of experimental & clinical cancer research : CR2019
ACE2 inhibits breast cancer angiogenesis via suppressing the VEGFa/VEGFR2/ERK pathway.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 164 papers.
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Who cites it
164 citing papers in PubMed.
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- Novel molecular biomarkers associated with Taxane-induced toxicities in women with breast cancer from the Brazilian Amazon.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- MiR-362-3p inhibits the proliferation, migration and EMT of gastric cancer cells by regulating the DEP-1/ERK signaling pathway.Scientific reports · 2026Article
- Angiotensin‑converting enzyme 2 as an immune and prognostic biomarker in colorectal cancer.Scientific reports · 2026Article
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- Celecoxib suppresses colorectal cancer growth by inhibiting propionyl-CoA carboxylase alpha chain-mediated epithelial-mesenchymal transition and angiogenesis.Gastroenterology report · 2026Article
- Clinical Significance and Potential Molecular Mechanisms of Angiotensin-Converting Enzyme 2 in Colorectal Cancer.World journal of oncology · 2026Article
- Sulfated Polysaccharide-Rich Fractions from Spirulina Platensis (SPPs) Exert Multi-Target Anticancer Activity in Non-Small Cell Lung Cancer (NSCLC) Cells.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Propofol attenuates angiogenesis by activating endoplasmic reticulum stress to suppress TFAP2C-driven VEGFA transcription.Apoptosis : an international journal on programmed cell death · 2026Article
- CCCdb: a comprehensive manually curated database for cell-cell communication in human and mouse.Nucleic acids research · 2026Article
- Diagnostic performance of vascular endothelial growth factor D in severity stratification of pediatric COVID-19 and multisystem inflammatory syndrome in children.Frontiers in immunology · 2026Article
- pH-Sensitive Long-Circulating Nanoliposomes with CU1 for Effective Against Lung Cancer.International journal of nanomedicine · 2026Article
- SARS-CoV2 and Anti-COVID-19 mRNA Vaccines: Is There a Plausible Mechanistic Link with Cancer?Cancers · 2025Review
- Enoxaparin alleviates preeclampsia by enhancing trophoblast function via the NSUN2-mediated mEuropean journal of medical research · 2025Article
- Methionine induced placental angiogenesis through activating WNT3A/CTNNB1-PIGF-VEGFR1 pathway.Cell communication and signaling : CCS · 2025Article
- Microenvironmental regulation and remodeling of breast cancer angiogenesis: from basic mechanisms to clinical therapeutic implications.Discover oncology · 2025Review
- Potential Therapeutic Actions of Flavonoids Present in Propolis That Modulate Vascular Endothelial Growth Factor Signaling to Regulate Angiogenesis.Phytotherapy research : PTR · 2025Review
104 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors.
Funding
Abstract
backgroundBreast cancer angiogenesis is key for metastasis and predicts a poor prognosis. Angiotensin-converting enzyme 2 (ACE2), as a member of the renin-angiotensin system (RAS), was reported to restrain the progression of hepatocellular carcinoma (HCC) and non-small cell lung cancer (NSCLC) through inhibiting angiogenesis. However, the relationship between ACE2 and breast cancer angiogenesis remains unclear.
methodsThe prognosis and relative gene selection were analysed using the GEPIA, GEO, TCGA and STRING databases. ACE2 expression in breast cancer tissue was estimated by reverse transcription-quantitative polymerase chain reaction (qPCR). Breast cancer cell migration, proliferation and angiogenesis were assessed by Transwell migration, proliferation, tube formation, and wound healing assays. The expression of vascular endothelial growth factor A (VEGFa) was detected by qPCR and Western blotting. The phosphorylation of vascular endothelial growth factor receptor 2 (VEGFR2), mitogen-activated protein kinase 1/2 (MEK1/2), and extracellular signal-regulated protein kinase 1/2 (ERK1/2) was examined by Western blotting. Breast cancer metastasis and angiogenesis in vivo were measured using a zebrafish model.
resultsACE2 was downregulated in breast cancer patients. Patients with higher ACE2 expression had longer relapse-free survival (RFS). In vitro, ACE2 inhibited breast cancer migration. Meanwhile, ACE2 in breast cancer cells inhibited human umbilical vascular endothelial cell (HUVEC) proliferation, tube formation and migration. In the zebrafish model, ACE2 inhibited breast cancer cell metastasis, as demonstrated by analyses of the number of disseminated foci and the metastatic distance. Neo-angiogenesis was also decreased by ACE2. ACE2 downregulated the expression of VEGFa in breast cancer cells. Furthermore, ACE2 in breast cancer cells inactivated the phosphorylation of VEGFR2, MEK1/2, and ERK1/2 in HUVECs.
conclusionsOur findings suggest that ACE2, as a potential resister to breast cancer, might inhibit breast cancer angiogenesis through the VEGFa/VEGFR2/ERK pathway.
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