SFMET

HGF/SF and MET in metastasis

Coordinatore	THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE    more  Organization address address: The Old Schools, Trinity Lane city: CAMBRIDGE postcode: CB2 1TN contact info Titolo: Ms. Nome: Dawn Cognome: Barker Email: send email Telefono: +44 1223 333543 Fax: +44 1223 332988
Nazionalità Coordinatore	United Kingdom [UK]
Sito del progetto	http://www2.mrc-lmb.cam.ac.uk/sfmet/index.html
Totale costo	4˙141˙339 €
EC contributo	2˙927˙008 €
Programma	FP7-HEALTH Specific Programme "Cooperation": Health
Code Call	FP7-HEALTH-2007-A
Funding Scheme	CP-FP
Anno di inizio	2008
Periodo (anno-mese-giorno)	2008-04-01   -   2011-09-30

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE  Organization address address: The Old Schools, Trinity Lane city: CAMBRIDGE postcode: CB2 1TN contact info Titolo: Ms. Nome: Dawn Cognome: Barker Email: send email Telefono: +44 1223 333543 Fax: +44 1223 332988	UK (CAMBRIDGE)	coordinator	0.00
2	CONSORZIO INTERUNIVERSITARIO RISONANZE MAGNETICHE DI METALLOPROTEINE PARAMAGNETICHE  Organization address address: Via Luigi Sacconi 6 city: SESTO FIORENTINO postcode: 50019 contact info Titolo: Prof. Nome: Ivano Cognome: Bertini Email: send email Telefono: +39 055 4574272 Fax: +39 055 4574271	IT (SESTO FIORENTINO)	participant	0.00
3	MAX-DELBRUCK-CENTRUM FUR MOLEKULARE MEDIZIN IN DER HELMHOLTZ-GEMEINSCHAFT  Organization address address: ROBERT ROSSLE STRASSE 10 city: BERLIN postcode: 13125 contact info Nome: Manuela Cognome: Adloff Email: send email Telefono: -94062204 Fax: -94062562	DE (BERLIN)	participant	0.00
4	UNIVERSITA DEGLI STUDI DI TORINO  Organization address address: Via Giuseppe Verdi 8 city: TORINO postcode: 10124 contact info Titolo: Prof. Nome: Maria Flavia Cognome: Di Renzo Email: send email Telefono: +39 011 9933343 Fax: +39 011 9933417	IT (TORINO)	participant	0.00

Mappa

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 Obiettivo del progetto (Objective)

'The growth and motility factor HGF/SF and its receptor MET define a paracrine signalling system which controls the migration of several cell lineages in embryogenesis and tissue repair. In a large number of human tumours, cancer cells hijack HGF/SF and MET signalling in order to invade adjacent tissue and initiate metastasis. The evidence for this is strong, broad and consistent and highlights HGF/SF and MET as key effectors of tumour invasion and primary targets for therapy. This proposal has two objectives. The first is to understand the mechanism by which HGF/SF and MET cause tumour invasion and, specifically: - how local hypoxia induces MET over-expression in tumour cells and how the MET - WNT and the MET - chemokine pathways cooperate in metastasis. The second aim is to develop MET therapeutics. These will include: (i) a protein antagonist built from a fragment of the ligand known as NK1, (ii) low molecular weight MET antagonists and, (iii) inhibitors of SHP-2, a critical effector of MET signalling. NK1 will be engineered as a receptor antagonist on the strength of available crystal structures. Low molecular weight MET antagonists and SHP-2 inhibitors will be developed on the strength of: - the availability of recombinant forms of the target proteins, - suitable screening methodologies and, - the results of initial screens that have provided robust proof of principle for both approaches. The proposal thus builds on strong progress in participating laboratories on the structure and function of HGF/SF and MET and fulfils the three key criteria described in the call for proposal ‘Understanding and fighting metastasis’, namely: (i) it addresses a key mechanism of dissemination of human tumours, (ii) contributes to understanding the interplay between the tumour microenvironment (the source of HGF/SF) and tumour cells (the cells that express the MET receptor) and, (iii) has considerable prospects of delivering novel therapeutics for metastatic cancer'