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NuSiCC SIGNED

Modelling the therapeutic potential of NUAK1 suppression in colorectal cancer

Total Cost €

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EC-Contrib. €

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Partnership

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 NuSiCC project word cloud

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

dependency    engineered    candidate    phosphor    therapy    wnt    gradually    requirement    inhibition    structural    sporadic    examine    europeans    model    cr    shrinks    druggable    energetic    occurs    little    myc    alternative    kills    withstand    mechanism    treatment    obviously    intervention    cell    therapeutic    viability    survival    kinase    preliminary    obligate    lacking    exhibit    enzymatic    levels    beta    consequently    data    metabolomics    biological    mouse    cancer    lab    excellent    therefor    crc    catenin    colorectal    depletion    overexpression    ark5    erodes    activation    170    attractive    effector    deplete    overexpressing    appears    strategies    strategy    suggesting    initiation    homeostasis    ectopic    genetic    owing    culture    whereas    absence    lack    genetically    gut    atp    proteomic    murphy    rates    nuak1    thoroughly    overexpressed    showed    signalling    lose    difficult    suppression    hyper    deregulation    tumours    unable    93    annually    cells    combination    tumour   

Project "NuSiCC" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITY OF GLASGOW 

Organization address
address: UNIVERSITY AVENUE
city: GLASGOW
postcode: G12 8QQ
website: www.gla.ac.uk

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 United Kingdom [UK]
 Project website https://www.gla.ac.uk/researchinstitutes/cancersciences/staff/danielmurphy/
 Total cost 183˙454 €
 EC max contribution 183˙454 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2015
 Funding Scheme MSCA-IF-EF-ST
 Starting year 2016
 Duration (year-month-day) from 2016-06-01   to  2018-05-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITY OF GLASGOW UK (GLASGOW) coordinator 183˙454.00

Map

 Project objective

Colorectal cancer (CRC) kills up to 170,000 Europeans annually. Although survival rates have improved gradually, new treatment strategies are certainly needed. Hyper-activation of WNT/Beta-catenin signalling occurs in up 93% of CRC cases and MYC appears to be an obligate effector of Beta-Catenin in the gut, making MYC an attractive target for therapeutic intervention. MYC, however, is difficult to target directly, owing to its lack of enzymatic activity or obviously druggable structural features. An alternative strategy is to target the biological consequences of MYC deregulation. The Murphy lab recently showed that MYC overexpressing tumour cells in culture exhibit an ectopic dependency on a little-known kinase called ARK5/NUAK1: whereas cells lacking MYC overexpression are able to withstand NUAK1 depletion or inhibition, cells with overexpressed MYC are unable to maintain energetic homeostasis in the absence of NUAK1, deplete their ATP levels, and consequently lose viability. We have therefor taken a genetic approach to examine the requirement for NUAK1 during tumour development in a genetically engineered mouse model of sporadic Beta-Catenin-driven CRC. Our preliminary results show that NUAK1 is required for CR tumour initiation and, more importantly, that NUAK1 depletion shrinks pre-existing tumours, suggesting that NUAK1 is an excellent candidate target for treatment of CRC. Based on these exciting preliminary data, I now propose to thoroughly evaluate NUAK1 as a target for therapy in CRC and to use a combination of proteomic, phosphor-proteomic and metabolomics analysis to determine the mechanism by which NUAK1 suppression erodes tumour cell viability.

 Publications

year authors and title journal last update
List of publications.
2018 Björn Kruspig, Tiziana Monteverde, Sarah Neidler, Andreas Hock, Emma Kerr, Colin Nixon, William Clark, Ann Hedley, Sarah Laing, Seth B. Coffelt, John Le Quesne, Craig Dick, Karen Vousden, Carla P. Martins, Daniel J. Murphy
The ERBB network facilitates KRAS-driven lung tumorigenesis
published pages: eaao2565, ISSN: 1946-6234, DOI: 10.1126/scitranslmed.aao2565
Science Translational Medicine 10/446 2019-06-13
2018 Jennifer Port, Nathiya Muthalagu, Meera Raja, Fatih Ceteci, Tiziana Monteverde, Björn Kruspig, Ann Hedley, Gabriela Kalna, Sergio Lilla, Lisa Neilson, Martina Brucoli, Katarina Gyuraszova, Jacqueline Tait-Mulder, Mokdad Mezna, Silvija Svambaryte, Amy Bryson, David Sumpton, Allan McVie, Colin Nixon, Martin Drysdale, Hiroyasu Esumi, Graeme I. Murray, Owen J. Sansom, Sara R. Zanivan, Daniel J. Murphy
Colorectal Tumors Require NUAK1 for Protection from Oxidative Stress
published pages: 632-647, ISSN: 2159-8274, DOI: 10.1158/2159-8290.CD-17-0533
Cancer Discovery 8/5 2019-06-13

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