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PXD060265

PXD060265 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMechanical confinement governs phenotypic plasticity in melanoma
DescriptionPhenotype switching is a form of cellular plasticity in which cancer cells reversibly move between two opposite extremes - proliferative versus invasive states. While it has long been hypothesised that such switching is triggered by external cues, the identity of these cues has remained elusive. Here, we demonstrate that mechanical confinement mediates phenotype switching through chromatin remodelling. Using a zebrafish model of melanoma coupled with human samples, we profiled tumor cells at the interface between the tumor and surrounding microenvironment. Morphological analysis of interface cells showed elliptical nuclei suggestive of mechanical confinement by adjacent tissue. Spatial and single-cell transcriptomics demonstrated that the interface cells adopted a gene program of neuronal invasion, including acquisition of an acetylated tubulin cage that protects the nucleus during migration. We identified the DNA-bending protein HMGB2 as a confinement-induced mediator of the neuronal state. HMGB2 is upregulated in confined cells, and quantitative modelling revealed that confinement prolongs contact time between HMGB2 and chromatin, leading to changes in chromatin configuration that favor the neuronal phenotype. Genetic disruption of HMGB2 showed that it regulates the trade-off between proliferative and invasive states, in which confined HMGB2high tumor cells are less proliferative but more drug resistant. Our results implicate the mechanical microenvironment as a mechanism driving phenotype switching in melanoma.
HostingRepositoryPRIDE
AnnounceDate2025-08-26
AnnouncementXMLSubmission_2025-08-26_15:33:26.290.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterZhuoning Li
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentBruker Daltonics timsTOF series
Dataset History
RevisionDatetimeStatusChangeLog Entry
02025-01-27 15:57:19ID requested
12025-08-26 15:33:26announced
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: LC-MS,HMGB2, melanoma
Contact List
Richard White
contact affiliationCancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY
contact emailrichard.white@ludwig.ox.uk
lab head
Zhuoning Li
contact affiliationMSKCC
contact emailliz2@mskcc.org
dataset submitter
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Dataset FTP location
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PRIDE project URI
Repository Record List
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