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PXD079448

PXD079448 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleCyclin Dependent Kinase 4 (CDK4) maintains cell cytoskeleton integrity and behavior in Triple Negative Breast Cancer (TNBC) cells
DescriptionCyclin-Dependent Kinase 4 (CDK4) is best known for its role in cell cycle progression, but its contribution to cellular architecture is less understood. Here, we identify CDK4 as a regulator of cytoskeletal homeostasis in triple-negative breast cancer (TNBC). CDK4 phosphorylates the RhoGAP Myo9b at serine 1935, enhancing its activity and suppressing RhoA–ROCK–mediated actomyosin contractility. Loss or inhibition of CDK4 disrupts cell morphology, destabilizes the actin cytoskeleton, and increases contractility, alongside collapse of the intermediate filament network, including vimentin disorganization and altered mitochondrial distribution. CDK4-deficient cells also show faster but less directed migration. In vivo, tumors derived from CDK4WT and CDK4KO MDA-MB-231 cells implanted in the mammary fat pad display elevated pMLC levels by IHC, consistent with increased contractility, while proteomic analysis reveals enrichment of cytoskeletal pathways. Transcriptomic analyses (SCAN-B, TCGA, I-SPY2) further show that low CDK4 activity correlates with enhanced EMT, migration, metastasis, and RhoA signaling programs in TNBC. Together, these findings establish CDK4 as an upstream regulator of cytoskeletal integrity, linking actin dynamics, intermediate filament organization, and cell behavior, and reveal a structural role beyond its canonical function in cell cycle control.
HostingRepositoryPRIDE
AnnounceDate2026-06-22
AnnouncementXMLSubmission_2026-06-22_06:20:57.823.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterLluis Fajas
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentOrbitrap Exploris 480
Dataset History
RevisionDatetimeStatusChangeLog Entry
02026-06-09 04:51:31ID requested
12026-06-22 06:20:58announced
Publication List
10.1101/2025.08.06.668850;
Keyword List
submitter keyword: Actin cytoskeleton,CDK4, cell migration, actomyosin contractility, Myo9b, Triple Negative Breast cancer (TNBC)
Contact List
Lluis Fajas Coll
contact affiliationCenter for Integrative Genomics, CIG, UNIL Sorge, CH1015 Lausanne, Switzerland
contact emaillluis.fajas@unil.ch
lab head
Lluis Fajas
contact affiliationUNIL
contact emaillluis.fajas@unil.ch
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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