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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.

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

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

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 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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