ArticlePLoS medicine2007
Vascular endothelial growth factor mediates intracrine survival in human breast carcinoma cells through internally expressed VEGFR1/FLT1.
Article in PLoS medicine, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 papers.
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Who cites it
140 citing papers in PubMed, 264 citations in OpenAlex.
- Antibodies blocking PlGF or VEGF interactions with the NRP1 receptor mediate antiproliferative effects.The Journal of biological chemistry · 2026Article
- Phase II trial of anlotinib-chemotherapy combination in pretreated HER2-negative metastatic breast cancer: therapeutic efficacy and proteomic biomarker profiling.NPJ breast cancer · 2026Article
- Antibodies blocking PlGF or VEGF interactions with the NRP1 receptor mediate anti-proliferative effects.bioRxiv : the preprint server for biology · 2025Article
- Pro-Angiogenic Bioactive Molecules in Vascular Morphogenesis: Integrating Endothelial Cell Dynamics.Current issues in molecular biology · 2025Review
- In vivo inhibition of angiogenesis by htsFLT01/MiRGD nano complex.Translational oncology · 2025Article
- Review
- VEGFR2 blockade inhibits glioblastoma cell proliferation by enhancing mitochondrial biogenesis.Journal of translational medicine · 2024Article
- Impact of Nintedanib and Anti-Angiogenic Agents on Uveal Melanoma Cell Behavior.Investigative ophthalmology & visual science · 2024Article
- Article
- IGF-1R targeting in cancer - does sub-cellular localization matter?Journal of experimental & clinical cancer research : CR · 2023Review
- Autocrine S100B in astrocytes promotes VEGF-dependent inflammation and oxidative stress and causes impaired neuroprotection.Cell biology and toxicology · 2023Article
- Efficacy of apatinib+radiotherapyThe British journal of radiology · 2023Article
- Article
- Regulation of VEGFR2 and AKT signaling by Musashi-2 in lung cancer.bioRxiv : the preprint server for biology · 2023Article
- Evaluation ofOncology letters · 2023Article
- KDM6B promotes gastric carcinogenesis and metastasis via upregulation of CXCR4 expression.Cell death & disease · 2022Article
- Review
- Evaluation of antitumor effects of VEGFR-2 inhibitor F16 in a colorectal xenograft model.Biotechnology letters · 2022Article
- Mediating EGFR-TKI Resistance by VEGF/VEGFR Autocrine Pathway in Non-Small Cell Lung Cancer.Cells · 2022Article
- Ang-Tie Angiogenic Pathway Is Distinctively Expressed in Benign and Malignant Adrenocortical Tumors.International journal of molecular sciences · 2022Article
80 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundWhile vascular endothelial growth factor (VEGF) expression in breast tumors has been correlated with a poor outcome in the pathogenesis of breast cancer, the expression, localization, and function of VEGF receptors VEGFR1 (also known as FLT1) and VEGFR2 (also known as KDR or FLK1), as well as neuropilin 1 (NRP1), in breast cancer are controversial. METHODS AND
findingsWe investigated the expression and function of VEGF and VEGF receptors in breast cancer cells. We observed that VEGFR1 expression was abundant, VEGFR2 expression was low, and NRP1 expression was variable. MDA-MB-231 and MCF-7 breast cancer cells, transfected with antisense VEGF cDNA or with siVEGF (VEGF-targeted small interfering RNA), showed a significant reduction in VEGF expression and increased apoptosis as compared to the control cells. Additionally, specifically targeted knockdown of VEGFR1 expression by siRNA (siVEGFR1) significantly decreased the survival of breast cancer cells through down-regulation of protein kinase B (AKT) phosphorylation, while targeted knockdown of VEGFR2 or NRP1 expression had no effect on the survival of these cancer cells. Since a VEGFR1-specific ligand, placenta growth factor (PGF), did not, as expected, inhibit the breast cancer cell apoptosis induced by siVEGF, and since VEGFR1 antibody also had no effects on the survival of these cells, we examined VEGFR1 localization. VEGFR1 was predominantly expressed internally in MDA-MB-231 and MCF-7 breast cancer cells. Specifically, VEGFR1 was found to be colocalized with lamin A/C and was expressed mainly in the nuclear envelope in breast cancer cell lines and primary breast cancer tumors. Breast cancer cells treated with siVEGFR1 showed significantly decreased VEGFR1 expression levels and a lack of VEGFR1 expression in the nuclear envelope.
conclusionsThis study provides, to our knowledge for the first time, evidence of a unique survival system in breast cancer cells by which VEGF can act as an internal autocrine (intracrine) survival factor through its binding to VEGFR1. These results may lead to an improved strategy for tumor therapy based on the inhibition of angiogenesis.
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