ArticleNature communications2021
Endothelial deletion of SHP2 suppresses tumor angiogenesis and promotes vascular normalization.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers.
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Who cites it
55 citing papers in PubMed, 99 citations in OpenAlex.
- Endothelial deletion of the neddylation E2 enzyme UBE2M inhibits tumor growth by promoting nonproductive angiogenesis.The Journal of clinical investigation · 2026Article
- SHP2 improves ovarian morphology and steroidogenic function in a rat PCOS model by modulating IRE1α/XBP1/NLRP3-mediated granulosa cell pyroptosis.Scientific reports · 2026Article
- Sustained nitric oxide production by engineered E. coli remodels the tumor microenvironment and potentiates immunotherapy.Nature biotechnology · 2026Article
- Targeting NRP1 in Endothelial Cells Facilitates the Normalization of Scar Vessels and Prevents Fibrotic Scarring.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- SHP2 regulates VEGFR2 Y1175/PLCγ signaling to impair tumor endothelial barrier stability.iScience · 2026Article
- SHP2 promotes osteosarcoma via regulating STAT3/TET3/HOXB2 signaling.Scientific reports · 2026Article
- RETRACTED: SHP2 improved Late-onset fetal growth restriction via modulating ROS/BRD4/PI3K/YAP/PIGF signaling induced angiogenesis.PloS one · 2026Article
- Tumor-associated endothelial cells in tumor immune escape and immunotherapy: multifaceted roles and treatment approaches.Biomarker research · 2025Review
- SHP2: A Redox-Sensitive Regulator Linking Immune Checkpoint Inhibitor Therapy to Cancer Treatment and Vascular Risk.Antioxidants (Basel, Switzerland) · 2025Review
- Tumor-Derived CCL16 Normalizes Tumor Vasculature through Macrophage ICAM-1 Receptor and Enhances Immunotherapy Efficacy in Hepatocellular Carcinoma.Cancer research · 2025Article
- Scaffolding Protein ENH Promotes Tumor Angiogenesis and Growth Through Macrophage Recruitment and Polarization.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- XPNPEP2 regulates angiogenesis via modulation of mitochondrial function through SLC25A6.Frontiers in cell and developmental biology · 2025Article
- [PHPS1 enhances PD-L1 serine phosphorylation by regulating ROS/SHP-2/AMPK activity to promote apoptosis of oral squamous cell carcinoma cells].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Leveraging CAR macrophages targeting c-Met for precision immunotherapy in pancreatic cancer: insights from single-cell multi-omics.Molecular medicine (Cambridge, Mass.) · 2024Article
- SHP2-Triggered Endothelial Cell Activation Fuels Estradiol-Independent Endometrial Sterile Inflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- PTPN11 is a potential biomarker for type 2 diabetes mellitus complicated with colorectal cancer.Scientific reports · 2024Article
- Combining RAS(ON) G12C-selective inhibitor with SHP2 inhibition sensitises lung tumours to immune checkpoint blockade.Nature communications · 2024Article
- Identification of differentially expressed tumour-related genes regulated by UHRF1-driven DNA methylation.Scientific reports · 2024Article
- Sexually Dimorphic Response to Hepatic Injury in Newborn Suffering from Intrauterine Growth Restriction.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SHP2 mediates the activities of multiple receptor tyrosine kinase signaling and its function in endothelial processes has been explored extensively. However, genetic studies on the role of SHP2 in tumor angiogenesis have not been conducted. Here, we show that SHP2 is activated in tumor endothelia. Shp2 deletion and pharmacological inhibition reduce tumor growth and microvascular density in multiple mouse tumor models. Shp2 deletion also leads to tumor vascular normalization, indicated by increased pericyte coverage and vessel perfusion. SHP2 inefficiency impairs endothelial cell proliferation, migration, and tubulogenesis through downregulating the expression of proangiogenic SRY-Box transcription factor 7 (SOX7), whose re-expression restores endothelial function in SHP2-knockdown cells and tumor growth, angiogenesis, and vascular abnormalization in Shp2-deleted mice. SHP2 stabilizes apoptosis signal-regulating kinase 1 (ASK1), which regulates SOX7 expression mediated by c-Jun. Our studies suggest SHP2 in tumor associated endothelial cells is a promising anti-angiogenic target for cancer therapy.
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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.