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PXD008229

PXD008229 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleColorectal tumors require NUAK1 for protection from oxidative stress
DescriptionNUAK1 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.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:42:02.883.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterSara Zanivan
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListphosphorylated residue; iodoacetamide derivatized residue
InstrumentLTQ Orbitrap Elite
Dataset History
RevisionDatetimeStatusChangeLog Entry
02017-11-17 08:01:34ID requested
12018-02-26 07:09:58announced
22018-03-08 00:10:24announcedUpdated publication reference for PubMed record(s): 29500295.
32024-10-22 04:42:08announced2024-10-22: Updated project metadata.
Publication List
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;
Keyword List
curator keyword: Biological, Biomedical
submitter keyword: oxidative stress
cystein oxidation
colorectal cancer
IAA
NUAK1
Contact List
Sara Zanivan
contact affiliationCRUK Beatson Institute
contact emails.zanivan@beatson.gla.ac.uk
lab head
Sara Zanivan
contact affiliationTumour Microenvironment & Proteomics
contact emails.zanivan@beatson.gla.ac.uk
dataset submitter
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Dataset FTP location
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PRIDE project URI
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