PXD060883-1

PXD060883 is an original dataset announced via ProteomeXchange.

Title	ERK signaling promotes IKKepsilon expression and oncogenic functions in pancreatic cancer cells in association with TBK1
Description	A variety of cancers utilize RAS-regulated signaling pathways to promote oncogenic phenotypes. A widely studied example is pancreatic cancer, where mutant KRAS signaling leads to activation of MEK/ERK kinases and downstream signaling which promotes oncogenic mechanisms, including cell proliferation. Importantly, ERK inhibitors have shown efficacy in some cancer clinical trials. Previously, others have studied the effects of the related kinases TBK1 and IKKε in pancreatic cancer where they have been shown to promote cell survival. Here, we show that RAS/MAPK signaling promotes expression of IKKε through control of protein stability and not through control of RNA levels. RNAseq analysis indicate that TBK1 and IKKε contribute to the expression of a subset of ERK-regulated genes. Potentially related to the effects on IKKε, proteomic analysis reveals that ERK functions to stabilize a relatively large set of proteins independent of RNA regulation. Knockdown of IKKε and TBK1 individually does not affect growth of MIA PaCa-2 pancreatic cancer cells, but dual knockdown significantly inhibits MIA PaCa-2 growth which is mediated through cell death. Concurrent silencing or inhibition of both TBK1 and IKKε also reduces tumor sphere growth in MIA PaCa-2 cells, correlating with a loss of stemness pathways found with RNAseq. The data suggest the importance of regulation of IKKε by ERK in pancreatic cancer cells and of the combined oncogenic activity of TBK1 and IKKε.
HostingRepository	PRIDE
AnnounceDate	2025-08-05
AnnouncementXML	Submission_2025-08-05_02:20:40.085.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Adam Graves
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion Lumos

Revision	Datetime	Status	ChangeLog Entry
0	2025-02-17 09:20:42	ID requested
⏵ 1	2025-08-05 02:20:40	announced

10.1016/J.JBC.2025.110535;

submitter keyword: ERK, IKKepsilon,MAPK, TBK1, KRAS

Albert Baldwin
contact affiliation	Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill
contact email	abaldwin@med.unc.edu
lab head
Adam Graves
contact affiliation	UNC Chapel Hill
contact email	adamcg@live.unc.edu
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/2025/08/PXD060883

PRIDE project URI

• PRIDE
  1. PXD060883
     1. Label: PRIDE project
     2. Name: ERK signaling promotes IKKepsilon expression and oncogenic functions in pancreatic cancer cells in association with TBK1