ArticleScience signaling2018
VEGF-neuropilin-2 signaling promotes stem-like traits in breast cancer cells by TAZ-mediated repression of the Rac GAP β2-chimaerin.
Article in Science signaling, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers, 1 of them a synthesis that pooled it.
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Who cites it
47 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Neuropilins as potential biomarkers in hepatocellular carcinoma: a systematic review of basic and clinical implications.Clinical and molecular hepatology · 2023Pooled it
- Discovery and Cryo-EM-Guided Development of a Neuropilin-2-Binding Aptamer for Receptor Antagonism.Journal of the American Chemical Society · 2026Article
- Rac1 in gastric cancer: a molecular driver of invasion, EMT, and therapeutic resistance.Journal of translational medicine · 2025Review
- Emerging Biomarkers in Urological Cancers: Angiogenesis and Damage-Associated Molecular Pattern Signaling.International journal of molecular sciences · 2025Review
- NRP2Inflammation and regeneration · 2025Article
- HDAC inhibitors modulate Hippo pathway signaling in hormone positive breast cancer.Clinical epigenetics · 2025Article
- A new Neu-a syngeneic model of spontaneously metastatic HER2-positive breast cancer.Clinical & experimental metastasis · 2024Article
- Neuropilin-2-expressing breast cancer cells mitigate radiation-induced oxidative stress through nitric oxide signaling.The Journal of clinical investigation · 2024Article
- Single-cell sequencing reveals VEGFR as a potential target for CAR-T cell therapy in chordoma.British journal of cancer · 2024Article
- Orchestrating Resilience: How Neuropilin-2 and Macrophages Contribute to Cardiothoracic Disease.Journal of clinical medicine · 2024Review
- VEGF signaling: Role in angiogenesis and beyond.Biochimica et biophysica acta. Reviews on cancer · 2024Review
- The inhibitory effect of apatinib on different small cell lung cancer cells and in lung cancer-bearing mice and patients.The clinical respiratory journal · 2024Article
- Apatinib has anti-tumor effects and induces autophagy in lung cancer cells with high expression of VEGFR-2.Iranian journal of basic medical sciences · 2024Article
- Inhibition of VEGF binding to neuropilin-2 enhances chemosensitivity and inhibits metastasis in triple-negative breast cancer.Science translational medicine · 2023Article
- Review
- Molecular Mechanisms and Future Implications of VEGF/VEGFR in Cancer Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Review
- Profiling and targeting cancer stem cell signaling pathways for cancer therapeutics.Frontiers in cell and developmental biology · 2023Review
- Review
- Role of Neuropilin-2-mediated signaling axis in cancer progression and therapy resistance.Cancer metastasis reviews · 2022Review
- Breast Cancer Stem Cells: Signaling Pathways, Cellular Interactions, and Therapeutic Implications.Cancers · 2022Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
The role of vascular endothelial growth factor (VEGF) signaling in cancer is not only well known in the context of angiogenesis but also important in the functional regulation of tumor cells. Autocrine VEGF signaling mediated by its co-receptors called neuropilins (NRPs) appears to be essential for sustaining the proliferation and survival of cancer stem cells (CSCs), which are implicated in mediating tumor growth, progression, and drug resistance. Therefore, understanding the mechanisms involved in VEGF-mediated support of CSCs is critical to successfully treating cancer patients. The expression of the Hippo effector TAZ is associated with breast CSCs and confers stem cell-like properties. We found that VEGF-NRP2 signaling contributed to the activation of TAZ in various breast cancer cells, which mediated a positive feedback loop that promoted mammosphere formation. VEGF-NRP2 signaling activated the GTPase Rac1, which inhibited the Hippo kinase LATS, thus leading to TAZ activity. In a complex with the transcription factor TEAD, TAZ then bound and repressed the promoter of the gene encoding the Rac GTPase-activating protein (Rac GAP) β2-chimaerin. By activating GTP hydrolysis, Rac GAPs effectively turn off Rac signaling; hence, the TAZ-mediated repression of β2-chimaerin resulted in sustained Rac1 activity in CSCs. Depletion of β2-chimaerin in non-CSCs increased Rac1 activity, TAZ abundance, and mammosphere formation. Analysis of a breast cancer patient database revealed an inverse correlation between β2-chimaerin and TAZ expression in tumors. Our findings highlight an unexpected role for β2-chimaerin in a feed-forward loop of TAZ activation and the acquisition of CSC properties.
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Registered trials
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