A5076596640- Angiogenesis and VEGF in Cancer
- Cell Adhesion Molecules Research
- Pancreatic and Hepatic Oncology Research
- Chromatin Remodeling and Cancer
- Renal cell carcinoma treatment
- Protease and Inhibitor Mechanisms
- Cancer, Hypoxia, and Metabolism
- Hippo pathway signaling and YAP/TAZ
- Lipid metabolism and disorders
- Wound Healing and Treatments
- Ubiquitin and proteasome pathways
- Cancer, Lipids, and Metabolism
- Platelet Disorders and Treatments
- Cellular Mechanics and Interactions
- Phagocytosis and Immune Regulation
- TGF-β signaling in diseases
- Atherosclerosis and Cardiovascular Diseases
- Cytokine Signaling Pathways and Interactions
- Vascular Tumors and Angiosarcomas
- Hearing Loss and Rehabilitation
- Hearing, Cochlea, Tinnitus, Genetics
- Cancer Cells and Metastasis
- Peptidase Inhibition and Analysis
- Ferroptosis and cancer prognosis
- Barrier Structure and Function Studies
Queen Mary University of London
2013-2023
Cancer Institute (WIA)
2014
Cancer Research UK
2003-2010
Pyrogenesis (Canada)
2010
Morpho (United States)
2010
Max Planck Institute for Molecular Biomedicine
2010
Institute of Cancer Research
2008
International Charter School
2006
Novartis (Switzerland)
2004
Novartis Institutes for BioMedical Research
2004
Highlights•Inducible deletion of endothelial ERG in mice causes defective angiogenesis•ERG controls vascular stability through Wnt/β-catenin signaling•β-catenin activation rescues the angiogenic defect vivo ERG-deficient mice•Overexpression stabilizes VEGF-induced angiogenesisSummaryBlood vessel is essential for embryonic development; adult, many diseases are associated with loss integrity. The ETS transcription factor drives expression VE-cadherin and junctional We show that constitutive...
Abstract The cytokine IL6 has a number of tumor-promoting activities in human and experimental cancers, but its potential as an angiogenic agent not been fully investigated. Here, we show that can directly induce vessel sprouting the ex vivo aortic ring model, well endothelial cell proliferation migration, with similar potency to VEGF. However, IL6-stimulated sprouts had defective pericyte coverage compared VEGF-stimulated vessels. mechanism action on pericytes involved stimulation Notch...
We have generated mice with a floxed fak allele under the control of keratin-14-driven Cre fused to modified estrogen receptor ( ER T2 ). 4-Hydroxy-tamoxifen treatment induced deletion in epidermis, and suppressed chemically skin tumor formation. Loss once benign tumors had formed inhibited malignant progression. Although was associated reduced migration keratinocytes vitro, we found no effect on wound re-epithelialization vivo. However, increased keratinocyte cell death observed after vitro...
Emerging evidence suggests that cancer cell metabolism can be regulated by cancer-associated fibroblasts (CAFs), but the mechanisms are poorly defined. Here we show CAFs regulate malignant through pathways under control of FAK. In breast and pancreatic patients find low FAK expression, specifically in stromal compartment, predicts reduced overall survival. mice, depletion a subpopulation regulates paracrine signals increase glycolysis tumour growth. Proteomic phosphoproteomic analysis our...
Tumor growth, tumor angiogenesis, and vascular endothelial growth factor (VEGF)-specific angiogenesis are all enhanced in beta(3)-integrin-null mice. Furthermore, cells isolated from beta(3)-null mice show elevated levels of Flk1 (VEGF receptor 2) expression, suggesting that beta(3)-integrin can control the amplitude VEGF responses by controlling or activity. We now signaling is required for seen Moreover, exhibit migration proliferation response to vitro, this phenotype requires signaling....
Abstract In adults, bone marrow‐derived cells (BMDC) can contribute to the structure of various non‐haematopoietic tissues, including skin. However, physiological importance these is unclear. This study establishes that epidermal are proliferative and, moreover, demonstrates for first time BMDC localize a known stem cell niche: CD34‐positive bulge region mouse hair follicles. addition, engraftment marrow into epidermis significantly increased in wounded skin, keratinocytes form colonies...
Both vascular endothelial growth factor receptors (VEGFR) and integrins are major regulators of VEGF-induced angiogenesis. Previous work has shown that β3 integrin can regulate negatively VEGFR2 expression. Here we show VEGF-mediated angiogenesis by limiting the interaction co-receptor NRP1 (neuropilin-1) with VEGFR2. In presence αvβ3 integrin, contributed minimally to angiogenic processes in vivo, ex vitro. Conversely, when expression is absent or low its function blocked RGD-mimetic...
Effective reepithelialization after injury is essential for correct wound healing. The upregulation of keratinocyte α3β1 integrin during suggests that this adhesion molecule involved in healing; however, its precise role process unknown. We have shown here retarded Itga3–/– mouse skin wounds due predominantly to repressed TGF-β1–mediated responses. Specifically, expression the inhibitor TGF-β1–signaling Smad7 was elevated keratinocytes. Indeed, vivo blockade increased rate and WT similar...
Abstract Expression of focal adhesion kinase (FAK) in endothelial cells (EC) is essential for angiogenesis, but how FAK phosphorylation at tyrosine-(Y)397 and Y861 regulate tumor angiogenesis vivo unknown. Here, we show that growth are constitutively reduced inducible, ECCre+;FAKY397F/Y397F–mutant mice. Conversely, ECCre+;FAKY861F/Y861F mice exhibit normal with an initial reduction recovered end-stage tumors. Mechanistically, FAK-Y397F ECs increased Tie2 expression, Vegfr2 decreased β1...
Abstract The overexpression of the protein tyrosine kinase, Focal adhesion kinase (FAK), in endothelial cells has implicated its requirement angiogenesis and tumour growth, but how pericyte FAK regulates is unknown. We show that growth multiple mouse models melanoma, lung carcinoma pancreatic B-cell insulinoma provide evidence loss enhances Gas6-stimulated phosphorylation receptor Axl with an upregulation Cyr61, driving enhanced growth. further derived Cyr61 instructs to elevate expression...
Beta3-integrin deficiency has been implicated in increasing levels of Flk-1 expression on endothelial cells and enhancing vascular growth factor (VEGF)-induced angiogenesis. We determined the role beta3-integrin mediating VEGF-A-induced blood vessel permeability through Flk-1.Using Miles assay, we demonstrated that plasma leakage was enhanced beta3-null mice when compared with wild-type controls. This not caused by any changes structure (as detected light or electron microscopy) cell-cell...
No single method has been universally adopted for identifying and isolating epidermal stem/progenitor cells, the emergence of new markers stem cell populations is worth exploring. Here we report, first time, that clusters basal keratinocytes at tips rete ridges in human palm, previously recognised as a major repository had very low levels desmoplakin protein mRNA expression, compared with cells sides or above dermal papillae. We found palm keratinocytes, selected by their ability to adhere...
Abstract The angiopoietin (Angpt)–TIE signaling pathway controls vascular maturation and maintains the quiescent phenotype of resting vasculature. contextual agonistic antagonistic Tie2 ligand ANGPT2 is believed to be exclusively produced by endothelial cells, disrupting constitutive ANGPT1–TIE2 destabilize microvasculature during pathologic disorders like inflammation cancer. However, scattered reports have also portrayed tumor cells as a source ANGPT2. Employing ISH-based detection ANGPT2,...