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MSCFate

Fate of mammary stem cells during tumorigenesis and clinical implications

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 MSCFate project word cloud

Explore the words cloud of the MSCFate project. It provides you a very rough idea of what is the project "MSCFate" about.

mouse    conditional    phenotype    resistance    origin    unbiased    found    biomarkers    investigation    cancer    contribution    expression    inhibitors    models    homeostasis    molecular    cell    generate    chemotherapy    coding    clinical    standard    suggests    pinpoint    reduces    progression    transformation    knew    e545k    combination    therapy    hotspot    accumulating    tracing    drug    eventual    portrait    tissue    preclinical    stem    poorly    model    vivo    genetic    patients    promotion    initiate    event    reports    breast    subunit    lineage    hyperactive    explored    therapies    mutations    tumors    panel    cells    procr    regulates    elucidate    pi3k    situ    perturb    acquires    ing    shown    mammary    h1047r    phosphoinositide    trigger    events    differentiation    tumor    biology    proliferation    oncogenic    heterogeneity    one    hypothesize    gene    mechanisms    questions    fate    msc    kinase    catalytic    responsible    hypothesis    consequently    ultimately    occurs    metastasis    pik3ca    first    perturbation   

Project "MSCFate" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITAT BASEL 

Organization address
address: PETERSPLATZ 1
city: BASEL
postcode: 4051
website: www.unibas.ch

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Switzerland [CH]
 Project website https://bentireslab.org/
 Total cost 175˙419 €
 EC max contribution 175˙419 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2016
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2017
 Duration (year-month-day) from 2017-09-01   to  2019-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITAT BASEL CH (BASEL) coordinator 175˙419.00

Map

 Project objective

One of the most challenging questions in breast cancer biology is to elucidate the origin of tumor heterogeneity and its contribution to therapy failure. Accumulating evidence suggests that the cell-of-origin, the cell that acquires the first oncogenic event, may define the molecular portrait of the resulting tumor. The fate of mammary Stem Cells (MSC) upon oncogenic perturbation has been poorly explored. Moreover, the Phosphoinositide 3-kinase (PI3K) pathway regulates proliferation/differentiation of MSC and is found hyperactive in breast cancer cells, for example through mutations in PIK3CA, the gene coding for its catalytic subunit. I hypothesize that expression of PIK3CA mutations will perturb mammary tissue homeostasis, initiate mammary cancer and trigger formation of stem-like cancer cells. Using state-of-the-art in situ genetic lineage tracing, I will determine the fate of MSC (identified recently as Procr cells) after conditional expression of PIK3CA hotspot mutations (H1047R, E545K). I will also characterize early molecular events responsible for promotion of transformation (Aim 1). When tumors develop, I will determine tumor phenotype and eventual progression to metastasis (Aim 2). Consequently, this study will generate a new mouse model of breast cancer that will be useful for preclinical studies. A panel of PI3K inhibitors is currently under Clinical investigation and clinical reports have shown that the combination of standard chemotherapy with PI3K inhibitors reduces tumor growth but drug-resistance often occurs. To identify resistance mechanisms to PI3K inhibitors, I will generate in vivo models of drug-resistance (Aim 3). My studies will use both hypothesis driven and unbiased approaches, they should: 1. better elucidate transformation of MSC and the resulting tumor heterogeneity, 2. pinpoint novel targets/biomarkers. Ultimately this knew knowledge should result in better therapies for patients.

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The information about "MSCFATE" are provided by the European Opendata Portal: CORDIS opendata.

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