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dc.contributor.authorBasu-Roy, Upal
dc.contributor.authorSeo, Eunjeong
dc.contributor.authorRamanathapuram, Lalitha
dc.contributor.authorRapp, Timothy B.
dc.contributor.authorPerry, Jennifer
dc.contributor.authorOrkin, Stuart Holland
dc.contributor.authorMansukhani, Alka
dc.contributor.authorBasilico, Claudio
dc.date.accessioned2013-04-18T20:41:34Z
dc.date.issued2011
dc.identifier.citationBasu-Roy, Upal, Eunjeong Seo, Lalitha Ramanathapuram, Timothy B. Rapp, Jennifer A. Perry, Stuart H. Orkin, Alka Mansukhani, and Claudio Basilico. 2011. Sox2 maintains self-renewal of tumor initiating cells in osteosarcomas. Oncogene 31(18): 2270-2282.en_US
dc.identifier.issn0950-9232en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10579096
dc.description.abstractTumors are thought to be sustained by a reservoir of self-renewing cells, termed tumor initiating cells or cancer stem cells. Osteosarcomas are high-grade sarcomas derived from osteoblast progenitor cells and are the most common pediatric bone malignancy. In this report we show that the stem cell transcription factor Sox2 is highly expressed in human and murine osteosarcoma cell lines as well as in tumor samples. Osteosarcoma cells have increased ability to grow in suspension as osteospheres, that are greatly enriched in expression of Sox2 and the stem cell marker, Sca-1. Depletion of Sox2 by shRNAs in independent murine osteosarcoma-derived cells drastically reduces their transformed properties in vitro and their ability to form tumors. Sox2-depleted osteosarcoma cells can no longer form osteospheres, and differentiate into mature osteoblasts. Concomitantly, they exhibit decreased Sca-1 expression and upregulation of the Wnt signaling pathway. Thus, despite other mutations, these tumor cells maintain a proliferative requirement for Sox2. Our data indicate that Sox2 is required for osteosarcoma cell self-renewal, and that Sox2 antagonizes the pro-differentiation Wnt pathway, that can in turn reduce Sox2 expression. These studies define Sox2 as a survival factor and a novel biomarker of self-renewal in osteosarcomas, and support a tumor suppressive role for the Wnt pathway in tumors of mesenchymal origin. Our findings could provide the basis for novel therapeutic strategies based on inhibiting Sox2 or enhancing Wnt signaling for the treatment of osteosarcomas.en_US
dc.language.isoen_USen_US
dc.relation.isversionofdoi:10.1038/onc.2011.405en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3243769/pdf/en_US
dash.licenseLAA
dc.subjectSox2en_US
dc.subjectosteosarcomaen_US
dc.subjectWnt signalingen_US
dc.subjectcancer stem cellen_US
dc.subjecttumor initiating cellen_US
dc.subjectmesenchymal tumorsen_US
dc.subjectdifferentiationen_US
dc.subjectsarcosphereen_US
dc.titleSox2 maintains self-renewal of tumor initiating cells in osteosarcomasen_US
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden_US
dc.relation.journalOncogeneen_US
dash.depositing.authorOrkin, Stuart Holland
dc.date.available2013-04-18T20:41:34Z
dc.identifier.doi10.1038/onc.2011.405*
dash.contributor.affiliatedPerry, Jennifer
dash.contributor.affiliatedOrkin, Stuart


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