@article{f6c2873a0bec40e2a6924305786e8b71,
title = "C/EBPβ-1 promotes transformation and chemoresistance in Ewing sarcoma cells",
abstract = "CEBPB copy number gain in Ewing sarcoma was previously shown to be associated with worse clinical outcome compared to tumors with normal CEBPB copy number, although the mechanism was not characterized. We employed gene knockdown and rescue assays to explore the consequences of altered CEBPB gene expression in Ewing sarcoma cell lines. Knockdown of EWS-FLI1 expression led to a decrease in expression of all three C/EBPβ isoforms while re-expression of EWS-FLI1 rescued C/EBPβ expression. Overexpression of C/EBPβ-1, the largest of the three C/EBPβ isoforms, led to a significant increase in colony formation when cells were grown in soft agar compared to empty vector transduced cells. In addition, depletion of C/EBPβ decreased colony formation, and re-expression of either C/EBPβ-1 or C/EBPβ-2 rescued the phenotype. We identified the cancer stem cell marker ALDH1A1 as a target of C/EBPβ in Ewing sarcoma. Furthermore, increased expression of C/EBPβ led to resistance to chemotherapeutic agents. In summary, we have identified CEBPB as an oncogene in Ewing sarcoma. Overexpression of C/EBPβ-1 increases transformation, upregulates expression of the cancer stem cell marker ALDH1A1, and leads to chemoresistance.",
keywords = "ALDH1A1, Biomarker, C/EBPβ, Chemoresistance, Ewing sarcoma",
author = "Gardiner, {Jamie D.} and Abegglen, {Lisa M.} and Xiaomeng Huang and Carter, {Bryce E.} and Schackmann, {Elizabeth A.} and Marcus Stucki and Paxton, {Christian N.} and Randall, {R. Lor} and Amatruda, {James F.} and Putnam, {Angelica R.} and Heinrich Kovar and Lessnick, {Stephen L.} and Schiffman, {Joshua D.}",
note = "Funding Information: We thank Kathi Byerline-Thayer for technical assistance, Alison Ondrus for experimental discussions, and Clint Mason for bioinformatics and statistical advice. We acknowledge the University of Utah's DNA Sequencing Core Facilities. This work was supported by the University of Utah Flow Cytometry Facility in addition to the National Cancer Institute (5P30CA042014-24, R21 CA187516-02). This work was also supported by the Cure Search for Children's Cancer, Damon Runyon Cancer Research Foundation, Children's Health Research Career Development Award (5K12HD001410-09), and the Sarcoma Alliance for Research through Collaboration Career Development Award. JDS holds an Edward B. Clark, MD Chair in Pediatric Research at the University of Utah and is a member of the Primary Children's Hospital (PCH) Pediatric Cancer Program, funded by the Intermountain Healthcare Foundation and the Primary Children's Hospital Foundation. The authors acknowledge the Sarcoma Disease Oriented Team (DOT) for its administrative coordination and support of sarcoma research at the University of Utah.Cure Search for Children's Cancer, Children's Health Research Career Development Award, the Sarcoma Alliance for Research through Collaboration Career Development Award, and R21 CA187516-02 (National Cancer Institute).",
year = "2017",
doi = "10.18632/oncotarget.14847",
language = "English (US)",
volume = "8",
pages = "26013--26026",
journal = "Oncotarget",
issn = "1949-2553",
publisher = "Impact Journals",
number = "16",
}