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ADHESWITCHES

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Adhesion switches in cancer and development from in vivo to synthetic biology

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... ver más

30/04/2019

UNIVERSITY OF TURK...

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

TURUN YLIOPISTO No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo FP7 notifico la concesión del proyecto el día 2019-04-30 No tenemos la información de la convocatoria

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1 Participantes

UNIVERSITY OF TURKU

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Líder del proyecto

TURUN YLIOPISTO No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 2M€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto 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.

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