PXD008229

PXD008229 is an original dataset announced via ProteomeXchange.

Title	Colorectal tumors require NUAK1 for protection from oxidative stress
Description	NUAK1 is a member of the AMPK family of kinases involved in regulation of cell adhesion, metabolism and stress responses. Our previous analysis revealed a requirement for NUAK1 to sustain viability when MYC is overexpressed. Human colorectal cancer (CRC) shows near uniform overexpression of MYC, suggesting that this cancer may be particularly amenable to NUAK1 inhibition. This work reveals that elevated NUAK1 expression in human CRC correlates with more aggressive disease, lymph node metastasis and reduced overall survival. Deletion of Nuak1 in murine intestines prevented outgrowth of colonic tumors driven by loss of Apc and KRas mutation, while depletion of Nuak1 in pre-existing tumors drove rapid tumor regression. Mechanistically, we show that NUAK1 promotes anti-oxidant gene expression by facilitating nuclear import of NRF2. Deletion or inhibition of NUAK1 renders cells vulnerable to oxidative stress and provision of exogenous anti-oxidants protects cells in culture and colonic tumors in situ from Nuak1 depletion.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:42:02.883.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Sara Zanivan
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Elite

Revision	Datetime	Status	ChangeLog Entry
0	2017-11-17 08:01:34	ID requested
1	2018-02-26 07:09:58	announced
2	2018-03-08 00:10:24	announced	Updated publication reference for PubMed record(s): 29500295.
⏵ 3	2024-10-22 04:42:08	announced	2024-10-22: Updated project metadata.

Port J, Muthalagu N, Raja M, Ceteci F, Monteverde T, Kruspig B, Hedley A, Kalna G, Lilla S, Neilson L, Brucoli M, Gyuraszova K, Tait-Mulder J, Mezna M, Svambaryte S, Bryson A, Sumpton D, McVie A, Nixon C, Drysdale M, Esumi H, Murray GI, Sansom OJ, Zanivan SR, Murphy DJ, Colorectal Tumors Require NUAK1 for Protection from Oxidative Stress. Cancer Discov, 8(5):632-647(2018) [pubmed]

10.1158/2159-8290.cd-17-0533;

curator keyword: Biological, Biomedical

submitter keyword: oxidative stress

cystein oxidation

colorectal cancer

IAA

NUAK1

Sara Zanivan
contact affiliation	CRUK Beatson Institute
contact email	s.zanivan@beatson.gla.ac.uk
lab head
Sara Zanivan
contact affiliation	Tumour Microenvironment & Proteomics
contact email	s.zanivan@beatson.gla.ac.uk
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2018/02/PXD008229

PRIDE project URI

• PRIDE
  1. PXD008229
     1. Label: PRIDE project
     2. Name: Colorectal tumors require NUAK1 for protection from oxidative stress