SHP2N

Characterization of nuclear SHP2 function in breast cancer progression and metastasis

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 Telefono: +41 616972982 Fax: +41 616973976
Nazionalità Coordinatore	Switzerland [CH]
Totale costo	199˙317 €
EC contributo	199˙317 €
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-2013-IEF
Funding Scheme	MC-IEF
Anno di inizio	2015
Periodo (anno-mese-giorno)	2015-03-01   -   2017-07-02

 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 Telefono: +41 616972982 Fax: +41 616973976	CH (BASEL)	coordinator	199˙317.60

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 Obiettivo del progetto (Objective)

Breast cancer is the most frequently diagnosed cancer in women with ~1.1 million worldwide cases. Despite intense study, in a significant fraction of women, tumor progression and disease relapse is inevitable underscoring a crucial gap in our understanding of these important hallmarks. Currently, little is known about the biochemical networks controlling these processes. The host lab has shown a fundamental role for the protein tyrosine phosphatase, SHP2, in tumor progression and metastasis in two aggressive breast cancer subtypes, human epidermal growth factor 2 (HER2) positive and triple negative breast cancer. Preliminary data in breast cancer cell lines revealed nuclear localization of SHP2 and proteomic analysis identified candidate nuclear substrates including nucleolin. However, whether a nuclear function of SHP2 and how SHP2 and its binding partners (i.e nucleolin) might impact breast cancer progression and metastasis remain unknown. This proposal will take advantage of original, state-of-the art technologies including multiphoton intravital imaging developed by the host laboratory to determine the nuclear function of SHP2 in normal mammary epithelial cells and during breast cancer progression and metastasis. Finally, it will validate nucleolin (and other identified candidates) as a SHP2 nuclear substrate and determine whether it is a critical downstream effector of SHP2 in breast cancer. Elucidation of the mechanisms driving tumor progression and metastasis is paramount for the development of novel therapeutic strategies.