PXD007909-2

PXD007909 is an original dataset announced via ProteomeXchange.

Title	The Ewing sarcoma secretome and its response to activation of Wnt/beta- catenin signaling
Description	Tumor: tumor microenvironment (TME) interactions are critical for tumor progression and the composition and structure of the local extracellular matrix (ECM) are key determinants of tumor metastasis. We recently reported that activation of Wnt/beta- catenin signaling in Ewing sarcoma cells induces widespread transcriptional changes that are associated with acquisition of a metastatic tumor phenotype. Significantly, ECM protein-encoding genes were found to be enriched among Wnt/beta-catenin induced transcripts, leading us to hypothesize that activation of canonical Wnt signaling might induce changes in the Ewing sarcoma secretome. To address this hypothesis, conditioned media from Ewing sarcoma cell lines cultured in the presence or absence of Wnt3a was collected for proteomic analysis. Label-free mass spectrometry was used to identify and quantify differentially secreted proteins. We then used in silico databases to identify only proteins annotated as secreted. Comparison of the secretomes of two Ewing sarcoma cell lines revealed numerous shared proteins, as well as a degree of heterogeneity, in both basal and Wnt-stimulated conditions. Gene set enrichment analysis of secreted proteins revealed that Wnt stimulation reproducibly resulted in increased secretion of proteins involved in ECM organization, ECM receptor interactions, and collagen formation. In particular, Wnt-stimulated Ewing sarcoma cells upregulated secretion of structural collagens, as well as matricellular proteins, such as the metastasis-associated protein, tenascin C (TNC). Interrogation of published databases confirmed reproducible correlations between Wnt/beta-catenin activation and TNC and COL1A1 expression in patient tumors. In summary, this first study of the Ewing sarcoma secretome reveals that Wnt/beta-catenin activated tumor cells upregulate secretion of ECM proteins. Such Wnt/beta-catenin mediated changes are likely to impact on tumor: TME interactions that contribute to metastatic progression.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:14:39.417.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Felipe da Veiga Leprevost
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue; deamidated residue
Instrument	Q Exactive HF

Revision	Datetime	Status	ChangeLog Entry
0	2017-10-09 01:37:20	ID requested
1	2018-02-07 12:37:35	announced
⏵ 2	2024-10-22 04:14:40	announced	2024-10-22: Updated project metadata.

10.1074/mcp.ra118.000596;

Hawkins AG, Basrur V, da Veiga Leprevost F, Pedersen E, Sperring C, Nesvizhskii AI, Lawlor ER, The Ewing Sarcoma Secretome and Its Response to Activation of Wnt/beta-catenin Signaling. Mol Cell Proteomics, 17(5):901-912(2018) [pubmed]

curator keyword: Biomedical

submitter keyword: Ewing sarcoma, Wnt/beta-catenin, Label-free mass spectrometry, Extracellular matrix, secretome, tumor microenvironment

Elizabeth R. Lawlor
contact affiliation	University of Michigan, 1600 Huron Parkway, NCRC Building 520, Rm1352, Ann Arbor, MI 48109-2800
contact email	elawlor@med.umich.edu
lab head
Felipe da Veiga Leprevost
contact affiliation	University of Michigan
contact email	leprevostfv@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD007909
     1. Label: PRIDE project
     2. Name: The Ewing sarcoma secretome and its response to activation of Wnt/beta- catenin signaling