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ADHESWITCHES: Adhesion switches in cancer and development: from in vivo to synthetic biology.

EU contribution: EUR 1 887 910

Objective: "Integrins are transmembrane cell adhesion receptors controlling cell proliferation and migration. Our objective is to gain fundamentally novel mechanistic insight into the emerging new roles of integrins in cancer and to generate a road map of integrin dependent pathways critical in mammary gland development and integrin signalling thus opening new targets for therapeutic interventions. We will combine an in vivo based translational approach with cell and molecular biological studies aiming to identify entirely novel concepts in integrin function using cutting edge techniques and synthetic-biology tools.

The specific objectives are:1) Integrin inactivation in branching morphogenesis and cancer invasion. Integrins regulate mammary gland development and cancer invasion but the role of integrin inactivating proteins in these processes is currently completely unknown. We will investigate this using genetically modified mice, ex-vivo organoid models and human tissues with the aim to identify beneficial combinational treatments against cancer invasion.

2) Endosomal adhesomes cross-talk between integrin activity and integrin inside-in signaling . We hypothesize that endocytosed active integrins engage in specialized endosomal signaling that governs cell survival especially in cancer. RNAi cell arrays, super-resolution STED imaging and endosomal proteomics will be used to investigate integrin signaling in endosomes.

3) Spatio-temporal co-ordination of adhesion and endocytosis. Several cytosolic proteins compete for integrin binding to regulate activation, endocytosis and recycling. Photoactivatable protein-traps and predefined matrix micropatterns will be employed to mechanistically dissect the spatio-temporal dynamics and hierarchy of their recruitment.

We will employ innovative and unconventional techniques to address three major unanswered questions in the field and significantly advance our understanding of integrin function in development and cancer."

Project completion date : 2019-04-30 12:00:00

Major organization : TURUN YLIOPISTO

Address : YLIOPISTONMAKI

TURUN YLIOPISTO

Country :Finland

Url : www.utu.fi

Financier : European Union (EU),

Financier address : European Union (EU)

Rue de la Loi 200/Wetstraat 200,

B-1049 Bruxelles/Brussels,

Belgium

Tel: 32-2-2999696, 2993085

Fax: 32-2-2961749

Url: ec.europa.eu/

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Publication:Mena Report
Date:Apr 14, 2015
Words:329
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