Title :

Dimerization of kringle 1 domain from hepatocyte growth factor/scatter factor provides a potent MET receptor agonist

Author(s) :

de Nola, Giovanni [Auteur]
Leclercq, Bérénice [Auteur]
Mougel, Alexandra [Auteur]
Taront, Solenne [Auteur]
Simonneau, Claire [Auteur]
Forneris, Federico [Auteur]
Adriaenssens, Eric [Auteur]
Hétérogénéité, Plasticité et Résistance aux Thérapies des Cancers = Cancer Heterogeneity, Plasticity and Resistance to Therapies - UMR 9020 - U 1277 [CANTHER]
Drobecq, Hervé [Auteur]
Iamele, Luisa [Auteur]
Dubuquoy, Laurent [Auteur]
Melnyk, Oleg [Auteur]
Gherardi, Ermanno [Auteur]
de Jonge, Hugo [Auteur]
Vicogne, Jérôme [Auteur]
Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL]

Journal title :

Life Science Alliance

Pages :

e202201424

Publisher :

Life Science Alliance LLC

Publication date :

2022-12-29

ISSN :

2575-1077

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Hepatocyte growth factor/scatter factor (HGF/SF) and its cognate receptor MET play several essential roles in embryogenesis and regeneration in postnatal life of epithelial organs such as the liver, kidney, lung, and ...
Show more >Hepatocyte growth factor/scatter factor (HGF/SF) and its cognate receptor MET play several essential roles in embryogenesis and regeneration in postnatal life of epithelial organs such as the liver, kidney, lung, and pancreas, prompting a strong interest in harnessing HGF/SF-MET signalling for regeneration of epithelial organs after acute or chronic damage. The limited stability and tissue diffusion of native HGF/SF, however, which reflect the tightly controlled, local mechanism of action of the morphogen, have led to a major search of HGF/SF mimics for therapy. In this work, we describe the rational design, production, and characterization of K1K1, a novel minimal MET agonist consisting of two copies of the kringle 1 domain of HGF/SF in tandem orientation. K1K1 is highly stable and displays biological activities equivalent or superior to native HGF/SF in a variety of in vitro assay systems and in a mouse model of liver disease. These data suggest that this engineered ligand may find wide applications in acute and chronic diseases of the liver and other epithelial organs dependent of MET activation.Show less >

Language :

Anglais

Popular science :

Non

Collections :

• Cancer Heterogeneity, Plasticity and Resistance to Therapies (CANTHER) - UMR 9020 - UMR 1277

Source :

Harvested from HAL

Submission date :

2024-03-12T04:33:30Z