Ptpl1 is a direct transcriptional target of ews-fli1 and modulates ewing's sarcoma tumorigenesis

Ptpl1 is a direct transcriptional target of ews-fli1 and modulates ewing's sarcoma tumorigenesis


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ABSTRACT Ewing's Sarcoma family tumors (ESFT) are characterized by a translocation t(11:22) forming an aberrant transcription factor EWS-FLI1. Protein tyrosine phosphatase L1 (PTPL1)


was identified as a gene upregulated by EWS-FLI1 in transfected cells by microarray. Our results show that PTPL1 is a transcriptional target of EWS-FLI1 both by chromatin immunoprecipitation


and promoter activation studies. We demonstrate that PTPL1 is highly expressed in ESFT cells and patient tumors compared with normal tissues, with a trend towards higher expression in


metastatic versus primary tumors. Reduction of PTPL1 protein in ESFT cells correlated with a significant reduction in both monolayer and soft-agar cell growth. In addition, these


PTPL1-reduced cells were more sensitive to etoposide-induced apoptosis than the controls. We therefore report a novel transcriptional activation of a phosphatase involved in the oncogenesis


of ESFT. Increasing interest in specific phosphatase inhibitors would allow PTPL1 to be evaluated as a therapeutic target in ESFT. Access through your institution Buy or subscribe This is a


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EWING SARCOMA BY ANTAGONISM OF EWS-FLI1-MEDIATED ENHANCER ACTIVATION Article 19 January 2023 SELECTIVE INHIBITION OF HDAC6 REGULATES EXPRESSION OF THE ONCOGENIC DRIVER EWSR1-FLI1 THROUGH THE


_EWSR1_ PROMOTER IN EWING SARCOMA Article Open access 03 August 2021 THE FLI PORTION OF EWS/FLI CONTRIBUTES A TRANSCRIPTIONAL REGULATORY FUNCTION THAT IS DISTINCT AND SEPARABLE FROM ITS


DNA-BINDING FUNCTION IN EWING SARCOMA Article Open access 18 June 2021 ABBREVIATIONS * ESFT: Ewing's Sarcoma family tumors * IGF-IR: insulin-like growth factor-I receptor * IRS-1:


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Olefsky JM . (1994). _J. Biol. Chem._, 269, 21244–21248. * Zwerner JP and May WA . (2001). _Oncogene_, 20, 626–633. Download references ACKNOWLEDGEMENTS We appreciate the technical help of


Hatice Özel Abaan, Kelsey McCarty, and Kamal Pathak, the assistance of Bob Fenton in the preparation of viral reagents, Marc Ladanyi for providing us unstained sections of the tissue


multiarrays, and the valuable suggestions of Anton Wellstein. This work generously supported by the Children's Cancer Foundation (JT) and R01 CA88004 (JT). AUTHOR INFORMATION AUTHORS


AND AFFILIATIONS * Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC, 20057, USA Ogan D Abaan, Amy Levenson, Osman Khan, Priscilla A Furth, Aykut


Üren & Jeffrey A Toretsky Authors * Ogan D Abaan View author publications You can also search for this author inPubMed Google Scholar * Amy Levenson View author publications You can also


search for this author inPubMed Google Scholar * Osman Khan View author publications You can also search for this author inPubMed Google Scholar * Priscilla A Furth View author publications


You can also search for this author inPubMed Google Scholar * Aykut Üren View author publications You can also search for this author inPubMed Google Scholar * Jeffrey A Toretsky View


author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Jeffrey A Toretsky. ADDITIONAL INFORMATION Supplementary Information


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ARTICLE CITE THIS ARTICLE Abaan, O., Levenson, A., Khan, O. _et al._ PTPL1 is a direct transcriptional target of EWS-FLI1 and modulates Ewing's Sarcoma tumorigenesis. _Oncogene_ 24,


2715–2722 (2005). https://doi.org/10.1038/sj.onc.1208247 Download citation * Received: 11 June 2004 * Revised: 28 September 2004 * Accepted: 28 September 2004 * Published: 14 March 2005 *


Issue Date: 14 April 2005 * DOI: https://doi.org/10.1038/sj.onc.1208247 SHARE THIS ARTICLE Anyone you share the following link with will be able to read this content: Get shareable link


Sorry, a shareable link is not currently available for this article. Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative KEYWORDS * PTPL1 * phosphatase *


EWS-FLI1 * Ewing's Sarcoma * ESFT