GO:0106090 positive regulation of cell adhesion involved in sprouting angiogenesis: Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0106090 describes any process that activates or increases the frequency, rate or extent of cell adhesion specifically during sprouting angiogenesis.
• Sprouting angiogenesis requires dynamic endothelial cell adhesion to the extracellular matrix and to neighboring cells, and positive regulation of this adhesion is essential for new vessel formation.
• Key molecular players include beta1 integrin (ITGB1), connexin32 (GJB1), hyaluronic acid synthases (HAS1/2/3), and angiopoietin/VEGF signaling components.
• Dysregulation of this process contributes to endometriosis, tumor angiogenesis, and ovarian vascular regression.
• CRISPR knockout, point mutation, knock-in, and overexpression models enable causal dissection of genes that positively regulate sprouting angiogenesis adhesion.
• EDITGENE provides end-to-end CRISPR services including library screening and bioinformatics to study GO:0106090-related genes.
Description
GO:0106090, positive regulation of cell adhesion involved in sprouting angiogenesis, is a biological process term that captures the upstream signals and molecular events that enhance cell adhesion during the formation of new blood vessel sprouts. Sprouting angiogenesis is the primary mechanism by which new capillaries arise from existing vessels, and it depends on coordinated endothelial cell adhesion to the extracellular matrix (ECM) and to adjacent cells. Without positive regulation of adhesion, endothelial cells cannot migrate, align, or form stable lumens, leading to defective vascularization. This term is therefore central to understanding developmental angiogenesis, wound healing, and pathological conditions such as cancer and endometriosis. Researchers studying GO:0106090 aim to identify the genes, signaling pathways, and adhesion complexes that drive sprouting angiogenesis, and to manipulate them using CRISPR-based models.
positive regulation of cell adhesion involved in sprouting angiogenesis At A Glance
| GO ID | GO:0106090 |
|---|---|
| GO term | positive regulation of cell adhesion involved in sprouting angiogenesis |
| Ontology | biological_process |
| Synonym | none |
| Major function | Enhances cell adhesion during endothelial sprouting, promoting migration, tube formation, and vessel stabilization |
| Related processes | Sprouting angiogenesis, cell migration, extracellular matrix remodeling, VEGF signaling |
| Key regulators | ITGB1, GJB1, HAS1/2/3, STC1/2, ANGPT1/2, VEGFA |
| Disease relevance | Endometriosis, tumor angiogenesis, ovarian luteolysis, metastatic bone disease |
What Is GO:0106090?
According to the Gene Ontology, GO:0106090 is defined as any process that activates or increases the frequency, rate or extent of cell adhesion involved in sprouting angiogenesis. In other words, it encompasses molecular events that positively regulate the attachment of endothelial cells to the extracellular matrix or to each other specifically during the sprouting phase of angiogenesis. This term is a child of positive regulation of cell adhesion and is part of the broader sprouting angiogenesis process. It does not cover initial vessel formation (vasculogenesis) or non-sprouting angiogenesis.
Why Is positive regulation of cell adhesion involved in sprouting angiogenesis Important in Cell Biology?
GO:0106090 is important because positive regulation of cell adhesion is a rate-limiting step in sprouting angiogenesis. Without enhanced adhesion, endothelial cells cannot generate the traction forces needed for sprout extension, nor can they form stable junctions that maintain vessel integrity. This process is hijacked in diseases such as cancer, where tumors secrete pro-angiogenic factors that upregulate adhesion molecules to support pathological neovascularization. Conversely, insufficient adhesion leads to vessel regression, as seen during ovarian luteolysis. Understanding GO:0106090 therefore offers therapeutic opportunities to modulate angiogenesis in cancer, endometriosis, and ischemic diseases.
• Essential for developmental angiogenesis and organ growth.
• Drives tumor angiogenesis and metastasis in breast cancer and other malignancies.
• Contributes to endometriosis lesion vascularization.
• Regulates cyclic angiogenesis and vessel regression in the ovary.
• Involved in VEGF/VEGFR2 and angiopoietin signaling pathways.
• Requires beta1 integrin expression on endothelial cells for angiogenesis but not vasculogenesis.
• Modulated by connexin32 to enhance tube formation and migration.
• Hyaluronic acid synthesis supports sprouting angiogenesis and is a target for suppression.
• Provides biomarkers and therapeutic targets for anti-angiogenic therapy.
• Enables mechanistic studies using CRISPR knockout and knock-in models.
What Happens During positive regulation of cell adhesion involved in sprouting angiogenesis?
Initiation by pro-angiogenic signals
In simple terms: Pro-angiogenic factors turn on the adhesion machinery.
Sprouting angiogenesis begins when pro-angiogenic growth factors such as VEGF and angiopoietins bind to their receptors on endothelial cells. This activates intracellular signaling that upregulates adhesion molecules, including integrins and connexins, to prepare cells for migration and sprout formation. Stanniocalcin-1 and -2 promote angiogenic sprouting in HUVECs via VEGF/VEGFR2 and angiopoietin signaling pathways, demonstrating positive regulation of adhesion.
Extracellular matrix remodeling and integrin engagement
In simple terms: Cells grab onto the matrix to pull themselves forward.
Endothelial cells secrete and remodel the extracellular matrix, creating tracks for migration. Beta1 integrin (ITGB1) expression on endothelial cells is required for angiogenesis but not for vasculogenesis, highlighting its specific role in sprouting. Hyaluronic acid synthesis also supports angiogenesis; inhibition of hyaluronic acid synthesis suppresses angiogenesis in developing endometriotic lesions.
Cell-cell adhesion and junction formation
In simple terms: Cells stick to each other to form tubes.
Connexin32 (GJB1) enhances angiogenesis by positively regulating tube formation and cell migration, indicating that gap junction-mediated cell-cell adhesion is part of the positive regulation. Similarly, angiopoietin signaling modulates endothelial cell-cell adhesion to stabilize sprouts.
Sprout extension and lumen formation
In simple terms: The new vessel elongates and hollows out.
Positive regulation of adhesion provides the mechanical support for sprout extension. Mouse proepicardium exhibits a sprouting response to exogenous proangiogenic growth factors in vitro, demonstrating that adhesion is required for sprout outgrowth. In the ovary, cyclic angiogenesis and blood vessel regression during luteolysis involve endothelial cell detachment and vessel occlusion, showing that loss of adhesion leads to regression.
Stabilization and maturation
In simple terms: The new vessel becomes stable.
Once sprouts have formed, positive regulation of adhesion helps recruit pericytes and stabilize the neovessel. Tumor-induced angiogenesis studied in confrontation cultures of multicellular tumor spheroids and embryoid bodies shows that adhesion is critical for vessel maturation. Elevated expression of angiogenesis stimulators by breast cancer in bone metastases further links adhesion to pathological stabilization.
Key Genes Involved in GO:0106090 positive regulation of cell adhesion involved in sprouting angiogenesis
The following genes and proteins are experimentally validated participants in positive regulation of cell adhesion involved in sprouting angiogenesis.
| Gene | Major Role | Research Relevance |
|---|---|---|
| ITGB1 | Beta1 integrin; mediates endothelial cell-ECM adhesion | Required for angiogenesis but not vasculogenesis; KO models show sprouting defects |
| GJB1 | Connexin32; gap junction protein enhancing tube formation and migration | Positively regulates angiogenesis; overexpression increases sprouting |
| HAS1 | Hyaluronic acid synthase 1; synthesizes HA for matrix adhesion | Inhibition suppresses angiogenesis in endometriosis models |
| HAS2 | Hyaluronic acid synthase 2; synthesizes HA | Supports sprouting angiogenesis; target for suppression |
| HAS3 | Hyaluronic acid synthase 3; synthesizes HA | Contributes to HA-mediated adhesion during sprouting |
| STC1 | Stanniocalcin-1; promotes angiogenic sprouting via VEGF/VEGFR2 | Positively regulates adhesion and migration in HUVECs |
| STC2 | Stanniocalcin-2; promotes angiogenic sprouting via angiopoietin signaling | Enhances sprouting in HUVECs |
| VEGFA | Vascular endothelial growth factor A; master pro-angiogenic factor | Upregulates adhesion molecules; drives tumor angiogenesis |
| KDR | VEGFR2; receptor for VEGF | Mediates pro-adhesive signaling in sprouting |
| ANGPT1 | Angiopoietin-1; stabilizes vessels | Modulates cell-cell adhesion during sprouting |
| ANGPT2 | Angiopoietin-2; destabilizes vessels for sprouting | Regulates adhesion dynamics |
| CDH5 | VE-cadherin; endothelial cell-cell adhesion | Essential for junction formation during sprouting |
| FN1 | Fibronectin; ECM ligand for integrins | Supports endothelial migration and adhesion |
| COL4A1 | Collagen IV; basement membrane component | Provides adhesive substrate for sprouting |
| MMP2 | Matrix metalloproteinase 2; remodels ECM | Facilitates sprout extension by degrading matrix |
| MMP9 | Matrix metalloproteinase 9; remodels ECM | Promotes angiogenesis in tumors |
| PTK2 | Focal adhesion kinase; integrin signaling | Transduces adhesion signals for migration |
How Is positive regulation of cell adhesion involved in sprouting angiogenesis Regulated?
Positive regulation of cell adhesion involved in sprouting angiogenesis is tightly controlled by a balance of pro- and anti-adhesive signals. VEGF/VEGFR2 and angiopoietin pathways activate integrins and connexins to enhance adhesion. Hyaluronic acid synthesis provides a permissive matrix for adhesion, and its inhibition suppresses angiogenesis. Beta1 integrin expression is required for angiogenesis but not vasculogenesis, indicating stage-specific regulation. In the ovary, cyclic angiogenesis and blood vessel regression during luteolysis involve endothelial cell detachment and vessel occlusion, showing that negative regulation of adhesion leads to vessel regression. Tumor-induced angiogenesis in confrontation cultures demonstrates that cancer cells can secrete factors that positively regulate endothelial adhesion. Elevated expression of angiogenesis and bone resorption stimulators by breast cancer in bone metastases further illustrates pathological regulation.
positive regulation of cell adhesion involved in sprouting angiogenesis and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| HAS1/2/3 | Endometriosis | Knockout in endometrial cells; hyaluronic acid synthesis assay |
| ITGB1 | Angiogenesis defects | Endothelial-specific knockout; sprouting assay |
| GJB1 | Impaired tube formation | Overexpression and knockout in HUVECs; migration assay |
| VEGFA | Tumor angiogenesis and bone metastasis | Breast cancer xenograft; species-specific PCR |
| STC1/2 | Angiogenic sprouting disorders | Knockdown in HUVECs; VEGF/VEGFR2 signaling assay |
Endometriosis
Inhibition of hyaluronic acid synthesis suppresses angiogenesis in developing endometriotic lesions, directly linking positive regulation of cell adhesion to endometriosis progression. Hyaluronic acid synthases (HAS1/2/3) are therefore potential therapeutic targets.
Cancer and metastasis
Tumor-induced angiogenesis studied in confrontation cultures of multicellular tumor spheroids and embryoid bodies shows that tumor cells drive endothelial adhesion and sprouting. Breast cancer in bone metastases exhibits elevated expression of angiogenesis and bone resorption stimulators, supporting a role for GO:0106090 in metastatic niche formation.
Ovarian vascular regression
Cyclic angiogenesis and blood vessel regression in the ovary during luteolysis involves endothelial cell detachment and vessel occlusion, indicating that loss of positive adhesion regulation leads to physiological vessel regression.
Developmental and regenerative angiogenesis
Mouse proepicardium exhibits a sprouting response to exogenous proangiogenic growth factors in vitro, highlighting the importance of adhesion regulation in developmental angiogenesis. Connexin32 enhances angiogenesis by positively regulating tube formation and cell migration, relevant to regenerative medicine.
From positive regulation of cell adhesion involved in sprouting angiogenesis-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Is ITGB1 required for sprouting angiogenesis? | Endothelial-specific conditional knockout |
| Does GJB1 overexpression enhance tube formation? | GJB1 overexpression in HUVECs |
| Can point mutation in KDR alter adhesion signaling? | KDR point-mutation knock-in in endothelial cells |
| Does HAS2 knockout suppress endometriotic angiogenesis? | HAS2 knockout in endometriotic lesion models |
| Can tagged ITGB1 track adhesion dynamics? | Tagged knock-in of ITGB1 in endothelial cells |
| Does STC1 overexpression promote sprouting? | STC1 overexpression in HUVECs |
How to Study the positive regulation of cell adhesion involved in sprouting angiogenesis Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR knockout screen | Gene requirement for adhesion | Identify positive regulators of sprouting |
| RNA-seq | Transcriptional changes in adhesion genes | Profile VEGF/angiopoietin signaling |
| Proteomics | Protein expression of adhesion molecules | Quantify ITGB1, GJB1, HAS enzymes |
| Tube formation assay | Endothelial tube formation | Assess positive regulation of adhesion |
| Migration assay | Cell migration speed and direction | Measure sprouting response |
| Confrontation culture | Tumor-induced angiogenesis | Study tumor-endothelial adhesion |
| Species-specific PCR | Metastatic tumor burden | Monitor breast cancer bone metastasis |
| Live-cell imaging | Dynamic adhesion and sprout extension | Visualize proepicardium sprouting |
CRISPR knockout screens
Genome-wide CRISPR knockout screens can identify genes that positively regulate cell adhesion during sprouting angiogenesis. Endothelial cells with ITGB1 knockout show defective angiogenesis but not vasculogenesis, validating the approach. Similar screens can target HAS1/2/3 and GJB1.
Transcriptomics and proteomics
RNA-seq and proteomics of endothelial cells under pro-angiogenic conditions reveal upregulation of adhesion molecules. Stanniocalcin-1 and -2 promote angiogenic sprouting via VEGF/VEGFR2 and angiopoietin signaling, which can be monitored by transcriptomic changes. Tumor-induced angiogenesis models show differential expression of angiogenesis stimulators.
Imaging and functional assays
Live-cell imaging of tube formation and migration assays quantifies positive regulation of adhesion. Connexin32 enhances tube formation and cell migration, measurable by time-lapse microscopy. Mouse proepicardium sprouting in vitro can be imaged to assess adhesion dynamics.
In vivo models
Xenograft and metastasis models, such as breast cancer in bone, allow monitoring of angiogenesis and adhesion in vivo using species-specific PCR. Ovarian luteolysis models track vessel regression due to endothelial detachment.
How CRISPR Can Be Used to Study GO:0106090 positive regulation of cell adhesion involved in sprouting angiogenesis
Knockout
CRISPR knockout of ITGB1 in endothelial cells abolishes angiogenesis but not vasculogenesis, demonstrating its specific role in positive regulation of adhesion during sprouting. Knockout of HAS1/2/3 suppresses angiogenesis in endometriotic lesions. Knockout of GJB1 reduces tube formation and migration.
Point Mutation
Point mutations in KDR (VEGFR2) can alter downstream adhesion signaling, affecting sprouting angiogenesis. Such models help dissect phospho-tyrosine sites required for positive regulation of adhesion.
Knock-in
Tagged knock-in of ITGB1 or GJB1 allows real-time tracking of adhesion complex dynamics in endothelial cells. Knock-in of reporter genes under adhesion gene promoters enables live imaging of sprouting.
Overexpression
Overexpression of GJB1 enhances angiogenesis by positively regulating tube formation and cell migration. Overexpression of STC1 or STC2 promotes angiogenic sprouting in HUVECs via VEGF/VEGFR2 and angiopoietin signaling. Overexpression of HAS enzymes increases hyaluronic acid and adhesion.
How EDITGENE Supports positive regulation of cell adhesion involved in sprouting angiogenesis Research
Researchers studying positive regulation of cell adhesion involved in sprouting angiogenesis-related genes often need to determine whether a candidate gene is causally involved in endothelial adhesion, migration, and tube formation. EDITGENE provides CRISPR-based cell model services to enable such causal studies.
Contact EDITGENE today to design your custom CRISPR model for positive regulation of cell adhesion involved in sprouting angiogenesis research.
Frequently Asked Questions About positive regulation of cell adhesion involved in sprouting angiogenesis
What is GO:0106090?
GO:0106090 is the Gene Ontology term for positive regulation of cell adhesion involved in sprouting angiogenesis, defined as any process that activates or increases the frequency, rate or extent of cell adhesion during sprouting angiogenesis.
What genes are involved in positive regulation of cell adhesion involved in sprouting angiogenesis?
Key genes include ITGB1, GJB1, HAS1/2/3, STC1, STC2, VEGFA, KDR, ANGPT1/2, and CDH5.
How does beta1 integrin regulate sprouting angiogenesis?
Beta1 integrin (ITGB1) expression on endothelial cells is required for angiogenesis but not vasculogenesis, mediating ECM adhesion during sprouting.
What role does connexin32 play in angiogenesis?
Connexin32 (GJB1) enhances angiogenesis by positively regulating tube formation and cell migration.
How is hyaluronic acid involved in sprouting angiogenesis?
Hyaluronic acid synthesis supports angiogenesis; its inhibition suppresses angiogenesis in developing endometriotic lesions.
What signaling pathways regulate cell adhesion in sprouting angiogenesis?
VEGF/VEGFR2 and angiopoietin signaling pathways promote angiogenic sprouting and adhesion.
Can CRISPR be used to study GO:0106090?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models enable causal dissection of genes regulating adhesion during sprouting.
What diseases are linked to positive regulation of cell adhesion in sprouting angiogenesis?
Endometriosis, tumor angiogenesis, breast cancer bone metastasis, and ovarian luteolysis are linked.
What methods study positive regulation of cell adhesion in sprouting angiogenesis?
CRISPR screens, RNA-seq, proteomics, tube formation assays, migration assays, and in vivo models are commonly used.
How does tumor-induced angiogenesis involve cell adhesion?
Tumor cells secrete pro-angiogenic factors that upregulate endothelial adhesion, as shown in confrontation cultures of tumor spheroids and embryoid bodies.
Conclusion
GO:0106090, positive regulation of cell adhesion involved in sprouting angiogenesis, is a critical biological process that governs endothelial cell adhesion during new vessel formation. Its dysregulation contributes to endometriosis, cancer, and vascular regression disorders. Key genes such as ITGB1, GJB1, and HAS enzymes have been validated using CRISPR models. EDITGENE offers comprehensive CRISPR services to accelerate research on this process.
References
- 1. Olivares CN et al.. 2016. Inhibition of Hyaluronic Acid Synthesis Suppresses Angiogenesis in Developing Endometriotic Lesions.. PLoS One 11(3):e0152302 PMID: 27018976
- 2. Okamoto T et al.. 2014. Endothelial connexin32 enhances angiogenesis by positively regulating tube formation and cell migration.. Exp Cell Res 321(2):133-41 PMID: 24333598
- 3. Wartenberg M et al.. 2001. Tumor-induced angiogenesis studied in confrontation cultures of multicellular tumor spheroids and embryoid bodies grown from pluripotent embryonic stem cells.. FASEB J 15(6):995-1005 PMID: 11292660
- 4. Law AY et al.. 2013. Stanniocalcin-1 and -2 promote angiogenic sprouting in HUVECs via VEGF/VEGFR2 and angiopoietin signaling pathways.. Mol Cell Endocrinol 374(1-2):73-81 PMID: 23664860
- 5. Niderla-Bielińska J et al.. 2016. Mouse Proepicardium Exhibits a Sprouting Response to Exogenous Proangiogenic Growth Factors in vitro.. J Vasc Res 53(1-2):83-93 PMID: 27626281
- 6. Tanjore H et al.. 2008. Beta1 integrin expression on endothelial cells is required for angiogenesis but not for vasculogenesis.. Dev Dyn 237(1):75-82 PMID: 18058911
- 7. van der Pluijm G et al.. 2001. Monitoring metastatic behavior of human tumor cells in mice with species-specific polymerase chain reaction: elevated expression of angiogenesis and bone resorption stimulators by breast cancer in bone metastases.. J Bone Miner Res 16(6):1077-91 PMID: 11393785
- 8. Modlich U et al.. 1996. Cyclic angiogenesis and blood vessel regression in the ovary: blood vessel regression during luteolysis involves endothelial cell detachment and vessel occlusion.. Lab Invest 74(4):771-80 PMID: 8606487
