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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:

insulin receptor substrate 1 * PTPL1: protein tyrosine phosphatase L1 * PTP: protein tyrosine phosphatase REFERENCES * Baer C, Nees M, Breit S, Selle B, Kulozik AE, Schaefer KL, Braun Y, Wai

D and Poremba C . (2004). _Int. J. Cancer_, 110, 687–694. * Banville D, Ahmad S, Stocco R and Shen SH . (1994). _J. Biol. Chem._, 269, 22320–22327. * Bompard G, Martin M, Roy C, Vignon F

and Freiss G . (2003). _J. Cell Sci._, 116, 2519–2530. * Bompard G, Puech C, Prebois C, Vignon F and Freiss G . (2002). _J. Biol. Chem._, 277, 47861–47869. * Dauphinot L, De Oliveira C,

Melot T, Sevenet N, Thomas V, Weissman BE and Delattre O . (2001). _Oncogene_, 20, 3258–3265. * de Alava E and Gerald WL . (2000). _J. Clin. Oncol._, 18, 204–213. * Deneen B, Hamidi H and

Denny CT . (2003a). _Cancer Res._, 63, 4268–4274. * Deneen B, Welford SM, Ho T, Hernandez F, Kurland I and Denny CT . (2003b). _Mol. Cell. Biol._, 23, 3897–3908. * Erdmann K . (2003). _Eur.

J. Biochem._, 270, 4789–4798. * Fan C, Li Q, Ross D and Engelhardt JF . (2003). _J. Biol. Chem._, 278, 2072–2080. * Fan C, Yang J and Engelhardt JF . (2002). _J. Cell Sci._, 115, 4843–4853.

* Freiss G, Puech C and Vignon F . (1998). _Mol. Endocrinol._, 12, 568–579. * Fukuma M, Okita H, Hata J and Umezawa A . (2003). _Oncogene_, 22, 1–9. * Gil-Henn H and Elson A . (2003). _J.

Biol. Chem._, 278, 15579–15586. * Grier HE, Krailo MD, Tarbell NJ, Link MP, Fryer CJ, Pritchard DJ, Gebhardt MC, Dickman PS, Perlman EJ, Meyers PA, Donaldson SS, Moore S, Rausen AR, Vietti

TJ and Miser JS . (2003). _N. Engl. J. Med._, 348, 694–701. * Hahm KB, Cho K, Lee C, Im YH, Chang J, Choi SG, Sorensen PH, Thiele CJ and Kim SJ . (1999). _Nat. Genet._, 23, 222–227. *

Houghton JA, Harwood FG, Gibson AA and Tillman DM . (1997). _Clin. Cancer Res._, 3, 2205–2209. * Irie S, Li Y, Kanki H, Ohyama T, Deaven LL, Somlo S and Sato TA . (2001). _DNA Sequence_, 11,

519–526. * Ivanov VN, Lopez Bergami P, Maulit G, Sato TA, Sassoon D and Ronai Z . (2003). _Mol. Cell. Biol._, 23, 3623–3635. * Khan J, Wei JS, Ringner M, Saal LH, Ladanyi M, Westermann F,

Berthold F, Schwab M, Antonescu CR, Peterson C and Meltzer PS . (2001). _Nat. Med._, 7, 673–679. * Komada Y, Inaba H, Zhou YW, Zhang XL, Tanaka S, Azuma E and Sakurai M . (1997). _Br. J.

Haematol._, 99, 325–330. * Kontny HU, Lehrnbecher TM, Chanock SJ and Mackall CL . (1998). _Cancer Res._, 58, 5842–5849. * Kovar H, Aryee DN, Jug G, Henockl C, Schemper M, Delattre O, Thomas

G and Gadner H . (1996). _Cell Growth Differ._, 7, 429–437. * Lee SH, Shin MS, Lee JY, Park WS, Kim SY, Jang JJ, Dong SM, Na EY, Kim CS, Kim SH and Yoo NJ . (1999). _J. Pathol._, 188,

207–212. * Lessnick SL, Dacwag CS and Golub TR . (2002). _Cancer Cell_, 1, 393–401. * Maekawa K, Imagawa N, Naito A, Harada S, Yoshie O and Takagi S . (1999). _Biochem. J._, 337 (Part 2),

179–184. * Mao X, Miesfeldt S, Yang H, Leiden JM and Thompson CB . (1994). _J. Biol. Chem._, 269, 18216–18222. * May WA, Gishizky ML, Lessnick SL, Lunsford LB, Lewis BC, Delattre O, Zucman

J, Thomas G and Denny CT . (1993). _Proc. Natl. Acad. Sci. USA_, 90, 5752–5756. * Mitsiades N, Poulaki V, Leone A and Tsokos M . (1999). _J. Natl. Cancer Inst._, 91, 1678–1684. * Murthy KK,

Clark K, Fortin Y, Shen SH and Banville D . (1999). _J. Biol. Chem._, 274, 20679–20687. * Myc A, Arscott PL, Bretz JD, Thompson NW and Baker Jr JR . (1999). _Endocrinology_, 140, 5431–5434.

* Nakai Y, Irie S and Sato TA . (2000). _Eur. J. Biochem._, 267, 7170–7175. * Nakatani F, Tanaka K, Sakimura R, Matsumoto Y, Matsunobu T, Li X, Hanada M, Okada T and Iwamoto Y . (2003). _J.

Biol. Chem._, 278, 15105–15115. * Nishimori H, Sasaki Y, Yoshida K, Irifune H, Zembutsu H, Tanaka T, Aoyama T, Hosaka T, Kawaguchi S, Wada T, Hata J, Toguchida J, Nakamura Y and Tokino T .

(2002). _Oncogene_, 21, 8302–8309. * Saras J, Claesson-Welsh L, Heldin CH and Gonez LJ . (1994). _J. Biol. Chem._, 269, 24082–24089. * Saras J, Engstrom U, Gonez LJ and Heldin CH . (1997a).

_J. Biol. Chem._, 272, 20979–20981. * Saras J, Franzen P, Aspenstrom P, Hellman U, Gonez LJ and Heldin CH . (1997b). _J. Biol. Chem._, 272, 24333–24338. * Seely BL, Reichart DR, Staubs PA,

Jhun BH, Hsu D, Maegawa H, Milarski KL, Saltiel AR and Olefsky JM . (1995). _J. Biol. Chem._, 270, 19151–19157. * Tanaka K, Iwakuma T, Harimaya K, Sato H and Iwamoto Y . (1997). _J. Clin.

Invest._, 99, 239–247. * Tanaka S, Ito T and Wands JR . (1996). _J. Biol. Chem._, 271, 14610–14616. * Thompson AD, Braun BS, Arvand A, Stewart SD, May WA, Chen E, Korenberg J and Denny C .

(1996). _Oncogene_, 13, 2649–2658. * Toretsky JA, Kalebic T, Blakesley V, LeRoith D and Helman LJ . (1997). _J. Biol. Chem._, 272, 30822–30827. * Toretsky JA, Thakar M, Eskenazi AE and

Frantz CN . (1999). _Cancer Res._, 59, 5745–5750. * Ungefroren H, Voss M, Jansen M, Roeder C, Henne-Bruns D, Kremer B and Kalthoff H . (1998). _Cancer Res._, 58, 1741–1749. * Uren A,

Merchant MS, Sun CJ, Vitolo MI, Sun Y, Tsokos M, Illei PB, Ladanyi M, Passaniti A, Mackall C and Toretsky JA . (2003). _Oncogene_, 22, 2334–2342. * Uslu R, Borsellino N, Frost P, Garban H,

Ng CP, Mizutani Y, Belldegrun A and Bonavida B . (1997). _Clin. Cancer Res._, 3, 963–972. * Watanabe G, Nishimori H, Irifune H, Sasaki Y, Ishida S, Zembutsu H, Tanaka T, Kawaguchi S, Wada T,

Hata J, Kusakabe M, Yoshida K, Nakamura Y and Tokino T . (2003). _Genes Chromosomes Cancer_, 36, 224–232. * Xiao S, Rose DW, Sasaoka T, Maegawa H, Burke Jr TR, Roller PP, Shoelson SE and

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