Biomaterial Database

Non-canonical NOTCH3 signalling limits tumour angiogenesis. 2017

Shuheng Lin, and Ana Negulescu, and Sirisha Bulusu, and Benjamin Gibert, and Jean-Guy Delcros, and Benjamin Ducarouge, and Nicolas Rama, and Nicolas Gadot, and Isabelle Treilleux, and Pierre Saintigny, and Olivier Meurette, and Patrick Mehlen

Apoptosis, Cancer and Development Laboratory-Equipe labellisée 'La Ligue', LabEx DEVweCAN, Centre de Recherche en Cancérologie de Lyon, INSERM U1052-CNRS UMR5286, Université de Lyon, Centre Léon Bérard, 69008 Lyon, France.

Notch signalling is a causal determinant of cancer and efforts have been made to develop targeted therapies to inhibit the so-called canonical pathway. Here we describe an unexpected pro-apoptotic role of Notch3 in regulating tumour angiogenesis independently of the Notch canonical pathway. The Notch3 ligand Jagged-1 is upregulated in a fraction of human cancer and our data support the view that Jagged-1, produced by cancer cells, is inhibiting the apoptosis induced by the aberrant Notch3 expression in tumour vasculature. We thus present Notch3 as a dependence receptor inducing endothelial cell death while this pro-apoptotic activity is blocked by Jagged-1. Along this line, using Notch3 mutant mice, we demonstrate that tumour growth and angiogenesis are increased when Notch3 is silenced in the stroma. Consequently, we show that the well-documented anti-tumour effect mediated by γ-secretase inhibition is at least in part dependent on the apoptosis triggered by Notch3 in endothelial cells.

UI	MeSH Term	Description	Entries
D008175	Lung Neoplasms	Tumors or cancer of the LUNG.	Cancer of Lung,Lung Cancer,Pulmonary Cancer,Pulmonary Neoplasms,Cancer of the Lung,Neoplasms, Lung,Neoplasms, Pulmonary,Cancer, Lung,Cancer, Pulmonary,Cancers, Lung,Cancers, Pulmonary,Lung Cancers,Lung Neoplasm,Neoplasm, Lung,Neoplasm, Pulmonary,Pulmonary Cancers,Pulmonary Neoplasm
D008810	Mice, Inbred C57BL	One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.	Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D009389	Neovascularization, Pathologic	A pathologic process consisting of the proliferation of blood vessels in abnormal tissues or in abnormal positions.	Angiogenesis, Pathologic,Angiogenesis, Pathological,Neovascularization, Pathological,Pathologic Angiogenesis,Pathologic Neovascularization,Pathological Angiogenesis,Pathological Neovascularization
D002289	Carcinoma, Non-Small-Cell Lung	A heterogeneous aggregate of at least three distinct histological types of lung cancer, including SQUAMOUS CELL CARCINOMA; ADENOCARCINOMA; and LARGE CELL CARCINOMA. They are dealt with collectively because of their shared treatment strategy.	Carcinoma, Non-Small Cell Lung,Non-Small Cell Lung Cancer,Non-Small Cell Lung Carcinoma,Non-Small-Cell Lung Carcinoma,Nonsmall Cell Lung Cancer,Carcinoma, Non Small Cell Lung,Carcinomas, Non-Small-Cell Lung,Lung Carcinoma, Non-Small-Cell,Lung Carcinomas, Non-Small-Cell,Non Small Cell Lung Carcinoma,Non-Small-Cell Lung Carcinomas
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071656	Receptor, Notch3	A notch receptor characterized by a large extracellular domain containing 34 EPIDERMAL GROWTH FACTOR-like repeats. It functions to regulate CELL DIFFERENTIATION; APOPTOSIS; and CELL PROLIFERATION. Mutations in the EGF repeats of Notch-3 are associated with CADASIL.	Neurogenic Locus Notch Homolog Protein 3,Notch-3 Protein,Notch-3 Receptor,Notch3 Protein,Notch3 Receptor,Notch 3 Protein,Notch 3 Receptor
D000072100	Jagged-1 Protein	A serrate-jagged protein that functions as a ligand for NOTCH RECEPTORS. It may regulate CELL DIFFERENTIATION in HEMATOPOIESIS and PHYSIOLOGIC ANGIOGENESIS. Mutations in the Jagged-1 gene are associated with ALAGILLE SYNDROME 1.	Alagille Syndrome Protein,CD339 Antigen,Jagged-1,Jagged1 Protein,Serrate-1 Protein,Serrate1 Protein,Antigen, CD339,Jagged 1,Jagged 1 Protein,Serrate 1 Protein
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D016923	Cell Death	The termination of the cell's ability to carry out vital functions such as metabolism, growth, reproduction, responsiveness, and adaptability.	Death, Cell
D042783	Endothelial Cells	Highly specialized EPITHELIAL CELLS that line the HEART; BLOOD VESSELS; and lymph vessels, forming the ENDOTHELIUM. They are polygonal in shape and joined together by TIGHT JUNCTIONS. The tight junctions allow for variable permeability to specific macromolecules that are transported across the endothelial layer.	Capillary Endothelial Cells,Lymphatic Endothelial Cells,Vascular Endothelial Cells,Capillary Endothelial Cell,Cell, Capillary Endothelial,Cell, Endothelial,Cell, Lymphatic Endothelial,Cell, Vascular Endothelial,Cells, Capillary Endothelial,Cells, Endothelial,Cells, Lymphatic Endothelial,Cells, Vascular Endothelial,Endothelial Cell,Endothelial Cell, Capillary,Endothelial Cell, Lymphatic,Endothelial Cell, Vascular,Endothelial Cells, Capillary,Endothelial Cells, Lymphatic,Endothelial Cells, Vascular,Lymphatic Endothelial Cell,Vascular Endothelial Cell