A5020394757- Wnt/β-catenin signaling in development and cancer
- Vascular Malformations Diagnosis and Treatment
- Angiogenesis and VEGF in Cancer
- Intracranial Aneurysms: Treatment and Complications
- Intracerebral and Subarachnoid Hemorrhage Research
- Hippo pathway signaling and YAP/TAZ
- Lymphatic System and Diseases
- Barrier Structure and Function Studies
- Kruppel-like factors research
- Cellular Mechanics and Interactions
- Cell Adhesion Molecules Research
- Congenital heart defects research
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Zebrafish Biomedical Research Applications
- Vascular Malformations and Hemangiomas
- Epigenetics and DNA Methylation
- Cancer Cells and Metastasis
- Cancer-related molecular mechanisms research
- Lymphatic Disorders and Treatments
- Pancreatic and Hepatic Oncology Research
- PARP inhibition in cancer therapy
- Muscle Physiology and Disorders
- Tissue Engineering and Regenerative Medicine
- Hedgehog Signaling Pathway Studies
- Signaling Pathways in Disease
IFOM
2015-2024
Italian Association for Cancer Research
2024
University of Milan
2009-2014
Wihuri Research Institute
2013
University of Eastern Finland
2013
University of Helsinki
2013
Korea Advanced Institute of Science and Technology
2013
Molecular Oncology (United States)
2006
Mario Negri Institute for Pharmacological Research
2000-2002
University of Insubria
2002
Receptor endocytosis is a fundamental step in controlling the magnitude, duration, and nature of cell signaling events. Confluent endothelial cells are contact inhibited their growth respond poorly to proliferative signals vascular factor (VEGF). In previous study, we found that association cadherin (VEC) with VEGF receptor (VEGFR) type 2 contributes density-dependent inhibition (Lampugnani, G.M., A. Zanetti, M. Corada, T. Takahashi, G. Balconi, F. Breviario, Orsenigo, Cattelino, R. Kemler,...
Junctional adhesion molecule (JAM) is an integral membrane protein that has been reported to colocalize with the tight junction molecules occludin, ZO-1, and cingulin. However, evidence for association of JAM these missing. Transfection Chinese hamster ovary cells (either alone or in combination occludin) resulted enhanced junctional localization both endogenous ZO-1 cotransfected occludin. Additionally, was coprecipitated detergent-insoluble fraction Caco-2 epithelial cells. A putative...
Endothelial adherens junctions maintain vascular integrity. Arteries and veins differ in their permeability but whether organization strength of vary has not been demonstrated vivo. Here we report that endothelial cadherin, an specific adhesion protein located at junctions, is phosphorylated Y658 Y685 vivo arteries under resting conditions. This difference due to shear stress-induced junctional Src activation veins. Phosphorylated endothelial-cadherin internalized ubiquitinated response...
Confluent endothelial cells respond poorly to the proliferative signals of VEGF. Comparing isogenic differing for vascular cadherin (VE-cadherin) expression only, we found that presence this protein attenuates VEGF-induced VEGF receptor (VEGFR) 2 phosphorylation in tyrosine, p44/p42 MAP kinase phosphorylation, and cell proliferation. VE-cadherin truncated β-catenin but not p120 binding domain is unable associate with VEGFR-2 induce its inactivation. β-Catenin–null are contact inhibited by...
The functional diversity of the arterial and venous endothelia is regulated through a complex system signalling pathways downstream transcription factors. Here we report that factor Sox17, which known as regulator endoderm hemopoietic differentiation, selectively expressed in arteries, not veins, mouse embryo postnatal retina adult. Endothelial cell-specific inactivation Sox17 accompanied by lack differentiation vascular remodelling results death utero. In retina, abrogation expression...
Pancreatic ductal adenocarcinoma (PDAC) is an aggressive cancer. The characteristic excessive stromatogenesis accompanying the growth of this tumor believed to contribute chemoresistance which, together with drug toxicity, results in poor clinical outcome. An increasing number studies are showing that gut microbiota and their metabolites implicated cancer pathogenesis, progression response therapies. In study we tested butyrate, a product dietary fibers' bacterial fermentation, whose...
Previously published reports support the concept that, besides promoting homotypic intercellular adhesion, cadherins may transfer intracellular signals. However, signaling pathways triggered by cadherin clustering and their biological significance are still poorly understood. We report herein that transfection of VE-cadherin (VEC) cDNA in VEC null endothelial cells induces actin rearrangement increases number vinculin positive adhesion plaques. expression augments level active Rac but...
Little is known about the molecular mechanisms that regulate organization of vascular lumen. In this paper we show lumen formation correlates with endothelial polarization. Adherens junctions (AJs) and VE-cadherin (VEC, encoded by CDH5) are required for apicobasal polarity in vitro during embryonic development. Silencing CDH5 gene expression leads to abrogation accompanied strong alterations lumenal structure. VEC co-distributes members Par complex (Par3 PKCzeta) needed activation PKCzeta....
Primitive lymphatic vessels are remodeled into functionally specialized initial and collecting lymphatics during development. Lymphatic endothelial cell (LEC) junctions in transform from a zipper-like to button-like pattern vessel development, but what regulates this process is largely unknown. Angiopoietin 2 (Ang2) deficiency leads abnormal vessels. Here we found that an ANG2-blocking antibody inhibited embryonic lymphangiogenesis, whereas endothelium-specific ANG2 overexpression induced...
Cerebral cavernous malformation (CCM) is a neurovascular familial or sporadic disease that characterised by capillary-venous cavernomas, and due to loss-of-function mutations any one of three CCM genes. Familial follows two-hit mechanism similar tumour suppressor genes, while in cavernomas only small fraction endothelial cells shows mutated We reported mouse models human patients, lining the lesions have different features from surrounding endothelium, as they express mesenchymal/stem-cell...
Background VE-cadherin is an endothelial specific, transmembrane protein, that clusters at adherens junctions where it promotes homotypic cell-cell adhesion. null mutation in the mouse results early fetal lethality due to altered vascular development. However, mechanism of action complex and, embryo, difficult define specific steps development which this protein involved. Methodology and Principal Findings In order study role system a more suitable model, we knocked down expression coding...
The microvasculature of the central nervous system includes blood-brain barrier (BBB), which regulates permeability to nutrients and restricts passage toxic agents inflammatory cells. Canonical Wnt/β-catenin signaling is responsible for early phases brain vascularization BBB differentiation. However, this signal declines after birth, other pathways able maintain integrity at postnatal stage are still unknown.Sox17 (SRY [sex-determining region Y]-box 17) constitutes a major downstream target...
Cerebral cavernous malformation (CCM) is a rare neurovascular disease that characterized by enlarged and irregular blood vessels often lead to cerebral hemorrhage. Loss-of-function mutations any of three genes results in CCM lesion formation; namely,