PTPSMETBC

Roles of SHP2 and other protein tyrosine phosphatases in metastatic breast cancer

Coordinatore	FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH    more  Organization address address: MAULBEERSTRASSE 66 city: BASEL postcode: 4058 contact info Titolo: Mrs. Nome: Dorothy Cognome: Searles Email: send email Telefono: +41 61 6972982 Fax: +41 61 6973976
Nazionalità Coordinatore	Switzerland [CH]
Totale costo	184˙709 €
EC contributo	184˙709 €
Programma	FP7-PEOPLE Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
Code Call	FP7-PEOPLE-2012-IEF
Funding Scheme	MC-IEF
Anno di inizio	2014
Periodo (anno-mese-giorno)	2014-03-01   -   2016-02-29

 Partecipanti

#	participant	country	role	EC contrib. [€]
1	FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL RESEARCH  Organization address address: MAULBEERSTRASSE 66 city: BASEL postcode: 4058 contact info Titolo: Mrs. Nome: Dorothy Cognome: Searles Email: send email Telefono: +41 61 6972982 Fax: +41 61 6973976	CH (BASEL)	coordinator	184˙709.40

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 Obiettivo del progetto (Objective)

'Breast cancer (BC) ranks second among cancer deaths in women. Each year, this disease is diagnosed in over one million women worldwide. Although progress has been made, we still do not understand the biology of BC at a level that would explain why certain patients react well to therapy, whereas for others the disease is recurrent, with an inexorable downhill course. This proposal focuses on the role of SHP2 and other protein tyrosine phosphatase (PTP) in BC metastasis and comprises three parallel approaches. The first aim is to address the roles of SHP2 in metastatic spread. The second assesses the merits of SHP2 as a therapeutic target in established BC metastases and the third will screen for other PTPs involved in metastatic BC. Virtually all cell signaling pathways are modulated by reversible protein tyrosine phosphorylation, which is regulated by two classes of enzymes, the protein tyrosine kinases (PTKs) and PTPs. Whereas the involvement of specific PTKs in BC has been well studied, the functions of specific PTPs in this disease are only now beginning to be elucidated. It has been discovered recently that SHP2 plays a fundamental role in tumor maintenance and progression in HER2-positive and triple-negative BCs, two subtypes associated with a poor prognosis. Importantly, SHP2 knockdown in established breast tumors blocked growth and reduced metastases. How does SHP2 knockdown in primary tumors reduce metastases? Can SHP2 inhibition in established metastases block their growth? Are other PTPs important for breast cancer metastases? To answer these questions, an intravital multiphoton microscope has been made for imaging fluorescently labeled metastatic BC cells expressing or lacking SHP2. These studies use state-of-the-art ex vivo and in vivo approaches to address the role of SHP2 and other PTPs in metastatic BC and should lead ultimately to the rational design of targeted therapies that will improve the clinical management of patients.'