PXD044029

PXD044029 is an original dataset announced via ProteomeXchange.

Title	Phosphoproteomic Changes Induced by Cell-Derived Matrix and Their Effect on Tumor Cell Migration and Cytoskeleton Remodeling
Description	Increased fibrotic extracellular matrix (ECM) deposition promotes tumor invasion, the first step of the metastatic cascade. Yet, the underlying mechanisms are poorly understood as conventional studies of tumor cell migration are often performed in 2D culture lacking the compositional and structural complexity of native ECM. Moreover, these studies frequently focus on select candidate pathways potentially overlooking other relevant changes in cell signaling. Here, we combine a cell-derived matrix (CDM) model with phosphotyrosine phosphoproteomic analysis to investigate tumor cell migration on fibrotic ECM relative to standard tissue culture plastic (TCP). Our results suggest that tumor cells cultured on CDMs migrate faster and in a more directional manner than their counterparts on TCP. These changes in migration correlated with decreased cell spreading and increased cell elongation. While the formation of phosphorylated focal adhesion kinase (pFAK)+ adhesion complexes did not vary between TCP and CDMs, time-dependent phosphoproteomic analysis identified that the SRC family kinase LYN may be differentially regulated. Pharmacological inhibition of LYN decreased tumor cell migration and cytoskeletal rearrangement on CDMs but also on TCP suggesting that LYN regulates tumor cell migration on CDMs in combination with other mechanisms. These data highlight how the combination of physicochemically complex in vitro systems with phosphoproteomics can help identify signaling mechanisms by which fibrotic ECM regulates tumor cell migration.
HostingRepository	PRIDE
AnnounceDate	2025-05-06
AnnouncementXML	Submission_2025-05-06_09:33:10.816.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD044029
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Tigist Tamir
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-24 04:57:55	ID requested
⏵ 1	2025-05-06 09:33:11	announced

10.1021/acsbiomaterials.3c01034;

10.6019/PXD044029;

Shimpi AA, Williams ED, Ling L, Tamir T, White FM, Fischbach C, Phosphoproteomic Changes Induced by Cell-Derived Matrix and Their Effect on Tumor Cell Migration and Cytoskeleton Remodeling. ACS Biomater Sci Eng, 9(12):6835-6848(2023) [pubmed]

submitter keyword: cytoskeleton, LYN signaling, adhesion, migration, phosphoproteomics,extracellular matrix

Forest White
contact affiliation	Massachusetts Institute of Technology, Department of Biological Engineering, David H Koch Institute for Integrative Cancer Research
contact email	fwhite@mit.edu
lab head
Tigist Tamir
contact affiliation	University of North Carolina at Chapel Hill, Department of Biochemistry and Biophysics
contact email	tytamir@mit.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD044029
     1. Label: PRIDE project
     2. Name: Phosphoproteomic Changes Induced by Cell-Derived Matrix and Their Effect on Tumor Cell Migration and Cytoskeleton Remodeling