PXD017543

PXD017543 is an original dataset announced via ProteomeXchange.

Title	Exosomes derived from mouse myoblasts expressing PAX3-FOXO1 oncogene protect recipient cells from oxidative stress and promote plasticity
Description	Rhabdomyosarcoma (RMS) is a highly malignant soft tissue sarcoma classified into two major histologic subtypes: embryonal (ERMS) and alveolar (ARMS). ARMS subtype is clinically more aggressive, and characterized by an oncogenic fusion protein PAX3-FOXO1 (P3F) that drives oncogenic cellular properties. To understand the role of the fusion oncoprotein in paracrine signaling, we focused on secreted exosomes, which have been demonstrated to contribute to metastasis in multiple tumor types. Mass spectrometry analysis of the protein cargo of exosomes isolated from C2C12 myoblasts transduced with P3F fusion gene revealed 52 deregulated proteins compared to control cells, with 26 enriched and 26 depleted proteins. Using both PANTHER gene classification and IPA software, we found that the main biological processes in which the 52 deregulated proteins are involved include “Catalytic activity”, “Binding”, “Metabolic process” and “Cellular process”. The pathways engaging the 26 enriched proteins include “14-3-3 mediated signaling”, “Cell cycle” and “ERK5, VEGF, IGF1and p70S6K signaling”. Main nodes in which deregulated exosome protein and miRNA intersected revealed pathways conferring protection from stress and promoting plasticity. Physiologically, exosomes derived from P3F-C2C12 cells activated ERK, 4-EBP1 and MMP-2, factors known to increase cell proliferation and invasion. In addition, they increased angiogenesis as evidenced by studies on HUVEC cells, and promoted stemness of MEFs and C2C12 cells. Treating stromal cells with exosomes from P3F-C2C12 cells protected them against effects of hydrogen peroxide (H2O2) in vitro, noting that P3F-C2C12 cells produce less ROS and are more resistant to induced exogenous oxidative stress as compared to control cells. Our findings highlight the role of P3F fusion protein in modulating exosome cargo to confer a protective effect on recipient cells against oxidative stress and promote plasticity and survival, potentially contributing to the known aggressive phenotype of the fusion gene-positive subtype of ARMS.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:25:58.730.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Wenjing Peng
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2020-02-17 03:05:40	ID requested
1	2021-09-08 09:46:28	announced
⏵ 2	2024-10-22 05:26:02	announced	2024-10-22: Updated project metadata.

10.3389/fonc.2020.01784;

Fahs A, Ramadan F, Ghamloush F, Ayoub AJ, Ahmad FA, Kobeissy F, Mechref Y, Zhao J, Zhu R, Hussein N, Saab R, Ghayad SE, Effects of the Oncoprotein PAX3-FOXO1 on Modulation of Exosomes Function and Protein Content: Implications on Oxidative Stress Protection and Enhanced Plasticity. Front Oncol, 10():1784(2020) [pubmed]

submitter keyword: exosomes, plasticity,Rhabdomyosarcoma, PAX3-FOXO1, oxidative stress

Yehia Mechref
contact affiliation	Department of Chemistry and Biochemistry, Texas Tech University, Lubbock, TX
contact email	yehia.mechref@ttu.edu
lab head
Wenjing Peng
contact affiliation	Texas Tech University
contact email	wenjing.peng@ttu.edu
dataset submitter

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/2021/09/PXD017543

PRIDE project URI

• PRIDE
  1. PXD017543
     1. Label: PRIDE project
     2. Name: Exosomes derived from mouse myoblasts expressing PAX3-FOXO1 oncogene protect recipient cells from oxidative stress and promote plasticity