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dc.creatorMancarella, Caterina
dc.creatorCaldoni, Giulia
dc.creatorRibolsi, Irene
dc.creatorParra, Alessandro
dc.creatorManara, Maria Cristina
dc.creatorMercurio, Arthur M.
dc.creatorMorrione, Andrea
dc.creatorScotlandi, Katia
dc.date.accessioned2021-11-09T15:40:29Z
dc.date.available2021-11-09T15:40:29Z
dc.date.issued2020-07-03
dc.identifier.citationMancarella C, Caldoni G, Ribolsi I, Parra A, Manara MC, Mercurio AM, Morrione A and Scotlandi K (2020) Insulin-Like Growth Factor 2 mRNA-Binding Protein 3 Modulates Aggressiveness of Ewing Sarcoma by Regulating the CD164-CXCR4 Axis. Front. Oncol. 10:994. doi: 10.3389/fonc.2020.00994
dc.identifier.issn2234-943X
dc.identifier.doihttp://dx.doi.org/10.34944/dspace/7056
dc.identifier.urihttp://hdl.handle.net/20.500.12613/7076
dc.description.abstractEwing sarcoma (EWS) is the second most common bone and soft tissue-associated malignancy in children and young adults. It is driven by the fusion oncogene EWS/FLI1 and characterized by rapid growth and early metastasis. We have previously discovered that the mRNA binding protein IGF2BP3 constitutes an important biomarker for EWS as high expression of IGF2BP3 in primary tumors predicts poor prognosis of EWS patients. We additionally demonstrated that IGF2BP3 enhances anchorage-independent growth and migration of EWS cells suggesting that IGF2BP3 might work as molecular driver and predictor of EWS progression. The aim of this study was to further define the role of IGF2BP3 in EWS progression. We demonstrated that high IGF2BP3 mRNA expression levels correlated with EWS metastasis and disease progression in well-characterized EWS tumor specimens. EWS tumors with high IGF2BP3 levels were characterized by a specific gene signature enriched in chemokine-mediated signaling pathways. We also discovered that IGF2BP3 regulated the expression of CXCR4 through CD164. Significantly, CD164 and CXCR4 colocalized at the plasma membrane of EWS cells upon CXCL12 stimulation. We further demonstrated that IGF2BP3, CD164, and CXCR4 expression levels correlated in clinical samples and the IGF2BP3/CD164/CXCR4 signaling pathway promoted motility of EWS cells in response to CXCL12 and under hypoxia conditions. The data presented identified CD164 and CXCR4 as novel IGF2BP3 downstream functional effectors indicating that the IGF2BP3/CD164/CXCR4 oncogenic axis may work as critical modulator of EWS aggressiveness. In addition, IGF2BP3, CD164, and CXCR4 expression levels may constitute a novel biomarker panel predictive of EWS progression.
dc.format.extent13 pages
dc.languageEnglish
dc.language.isoeng
dc.relation.ispartofFaculty/ Researcher Works
dc.relation.haspartFrontiers in Oncology, Vol. 10
dc.relation.isreferencedbyFrontiers Media
dc.rightsAttribution CC BY
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectIGF2BP3
dc.subjectMetastases
dc.subjectCD164
dc.subjectCXCR4
dc.subjectEwing sarcoma
dc.titleInsulin-Like Growth Factor 2 mRNA-Binding Protein 3 Modulates Aggressiveness of Ewing Sarcoma by Regulating the CD164-CXCR4 Axis
dc.typeText
dc.type.genreJournal article
dc.description.departmentBiology
dc.relation.doihttps://doi.org/10.3389/fonc.2020.00994
dc.ada.noteFor Americans with Disabilities Act (ADA) accommodation, including help with reading this content, please contact scholarshare@temple.edu
dc.description.schoolcollegeTemple University. College of Science and Technology
dc.creator.orcidMorrione|0000-0002-2319-7884
dc.temple.creatorMorrione, Andrea
refterms.dateFOA2021-11-09T15:40:29Z


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