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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

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

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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