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SelectiveTGFb-inhib SIGNED

Pro-tumorigenic effects of TGFb - elucidation of mechanisms and development of selective inhibitors

Total Cost €

0

EC-Contrib. €

0

Partnership

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 SelectiveTGFb-inhib project word cloud

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

tbrii    intracellular    molecular    acute    elucidate    interactors    pro    whereby    later    cohorts    kinase    transition    models    selective    systematic    embryonal    tgfb    tumorigenic    tyrosine    selectively    functional    src    think    activation    mesenchymal    surveillance    animal    domain    suppression    signaling    inhibition    induction    weight    compartment    tissue    tumorigenesis    homeostasis    activates    transforming    cancer    cell    cleaved    cells       multifunctional    suppress    vivo    patient    cytokine    activated    modifications    emt    angiogenesis    arrest    treatment    thereby    receptor    suppressor    stimulation    plan    identity    overexpressed    inhibit    cellular    tumor    patients    fibroblasts    posttranslational    apoptosis    survival    candidate    epithelial    functions    biomarkers    attempt    severe    suppressive    mechanisms    inhibitors    screen    perform    phosphatidylinositol    complete    tbri    mechanism    invasiveness    migration    nucleus    metastasis    immune   

Project "SelectiveTGFb-inhib" data sheet

The following table provides information about the project.

Coordinator
UPPSALA UNIVERSITET 

Organization address
address: VON KRAEMERS ALLE 4
city: UPPSALA
postcode: 751 05
website: www.uu.se

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 Sweden [SE]
 Total cost 2˙500˙000 €
 EC max contribution 2˙500˙000 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2017-ADG
 Funding Scheme ERC-ADG
 Starting year 2018
 Duration (year-month-day) from 2018-11-01   to  2023-10-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UPPSALA UNIVERSITET SE (UPPSALA) coordinator 2˙500˙000.00

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 Project objective

Transforming growth factor-b (TGFb) is a multifunctional cytokine which has important functions during embryonal development and in tissue homeostasis. In cancer, TGFb is often overexpressed and has both tumor suppressor effects (induction of growth arrest and apoptosis) and tumor promoting effects (stimulation of epithelial-mesenchymal transition (EMT) of tumor cells, stimulation of angiogenesis and cancer associated fibroblasts, and suppression of immune surveillance). Our aim is to elucidate the mechanisms for the pro-tumorigenic effects of TGFb and to develop selective inhibitors which can be used to suppress tumor invasiveness and metastasis in animal models, and later on for treatment of patients with advanced cancer. We think it is important to develop selective inhibitors, which do not affect the tumor suppressive effects of TGFb, since complete inhibition of TGFb may cause severe side effects and may even promote tumorigenesis. We plan to: 1. perform a systematic analysis of posttranslational modifications and interactors of the TGFb receptor I (TbRI) and II (TbRII), and determine their functional importance for the induction of various pro-tumorigenic pathways; 2. determine the mechanism whereby TGFb activates the tyrosine kinase Src, and its role in invasiveness and metastasis; 3. attempt to selectively inhibit the activation of phosphatidylinositol 3´-kinase by TGFb, in order to inhibit tumor cell survival and migration; 4. elucidate the functional role in the nucleus of the cleaved intracellular domain of TbRI, and attempt to inhibit its formation and thereby tumor metastasis; 5. determine the cellular compartment where the pro-tumorigenic signaling pathways are activated; 6. elucidate mechanisms for TGFb-induced EMT and develop candidate low molecular weight inhibitors that we have obtained from a screen, aiming at using them in vivo to suppress metastasis; 7. develop biomarkers to identity patient cohorts for treatment with selective TGFb inhibitors.

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