PXD050961

PXD050961 is an original dataset announced via ProteomeXchange.

Title	Spike-in enhanced phosphoproteomics uncovers synergistic signaling responses to MEK inhibition in colon cancer cells
Description	Targeted kinase inhibitors are a cornerstone of cancer therapy, but their success is often hindered by the complexity of cellular signaling networks that can lead to resistance. Overcoming this challenge necessitates a deep understanding of cellular signaling responses. While standard global phosphoproteomics offers extensive insights, lengthy processing times, the complexity of data interpretation, and frequent omission of crucial phosphorylation sites limit its utility. Here, we combine data-independent acquisition (DIA) with spike-in of synthetic heavy stable isotope-labeled phosphopeptides to facilitate the targeted detection of particularly informative phosphorylation sites. Our spike-in enhanced detection in DIA (SPIED-DIA) approach integrates the improved sensitivity of spike-in-based targeted detection with the discovery potential of global phosphoproteomics into a simple workflow. We employed this method to investigate synergistic signaling responses in colorectal cancer cell lines following MEK inhibition. Our findings highlight that combining MEK inhibition with growth factor stimulation synergistically activates JNK signaling in HCT116 cells. This synergy emphasizes the therapeutic potential of concurrently targeting MEK and JNK pathways, as evidenced by the significantly impaired growth of HCT116 cells when treated with both inhibitors. These results demonstrate that SPIED-DIA effectively identifies synergistic signaling responses in colorectal cancer cells, presenting a valuable tool for uncovering new therapeutic targets and strategies in cancer treatment.
HostingRepository	PRIDE
AnnounceDate	2025-03-11
AnnouncementXML	Submission_2025-03-11_08:32:09.181.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mirjam van Bentum
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	timsTOF Pro 2

Revision	Datetime	Status	ChangeLog Entry
0	2024-03-25 10:42:38	ID requested
⏵ 1	2025-03-11 08:32:09	announced

Dataset with its publication pending

submitter keyword: Caco2, Phosphoproteomics, Colorectal cancer, MEK inhibition, HCT116, DLD-1,DIA, SPIED-DIA

Matthias Selbach
contact affiliation	Proteome Dynamics, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany
contact email	Matthias.selbach@mdc-berlin.de
lab head
Mirjam van Bentum
contact affiliation	Max Delbruck Centre for Molecular Medicine Berlin
contact email	Mirjam.vanbentum@mdc-berlin.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD050961
     1. Label: PRIDE project
     2. Name: Spike-in enhanced phosphoproteomics uncovers synergistic signaling responses to MEK inhibition in colon cancer cells