PXD060265 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Mechanical confinement governs phenotypic plasticity in melanoma |
Description | Phenotype 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. |
HostingRepository | PRIDE |
AnnounceDate | 2025-08-26 |
AnnouncementXML | Submission_2025-08-26_15:33:26.290.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Zhuoning Li |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Bruker Daltonics timsTOF series |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2025-01-27 15:57:19 | ID requested | |
⏵ 1 | 2025-08-26 15:33:26 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: LC-MS,HMGB2, melanoma |
Contact List
Richard White |
contact affiliation | Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY |
contact email | richard.white@ludwig.ox.uk |
lab head | |
Zhuoning Li |
contact affiliation | MSKCC |
contact email | liz2@mskcc.org |
dataset submitter | |
Full Dataset Link List
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/PXD060265 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD060265
- Label: PRIDE project
- Name: Mechanical confinement governs phenotypic plasticity in melanoma