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IGF2 is critical for tumorigenesis by synovial sarcoma oncoprotein SYT-SSX1

Oncogene volume 25, pages 1042–1052 (2006)Cite this article

Abstract

Synovial sarcoma is an aggressive soft tissue tumor characterized by a specific chromosomal translocation between chromosome 18 and X. This translocation can generate a fusion transcript encoding SYT-SSX1, a transforming oncoprotein. We present evidence that SYT-SSX1 induces insulin-like growth factor II expression in fibroblast cells. SYT-SSX2, a fusion also frequently found in synovial sarcoma, is necessary for maintaining Igf2 expression in the synovial sarcoma cell line, and the increased IGF2 synthesis protects cells from anoikis and is required for tumor formation in vivo. We also found a loss of imprinting (LOI) for Igf2 in a limited number of primary synovial sarcomas despite demethylation of CpG dinucleotides critical for maintaining imprinting. These findings suggest that inhibition of the IGF2/IGF1-R signaling pathway may represent a significant therapeutic modality for treating synovial sarcoma.

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Acknowledgements

We thank Dr Robert A Weinberg at the Whitehead Institute for initial support and critical evaluation of the work. We thank Andy Beckler for earlier participation of the work. We are grateful for Dr Colin S Cooper for sending SYT and SYT-SSX1 plasmids as well as synovial sarcoma cell lines. We thank Juanita Perera, Qing Liu for technical help. This work is in part supported by strategic planing of University of Rochester as well as a Discovery Fund from James P Wilmont Cancer Center of University of Rochester.

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Authors and Affiliations

  1. Department of Biomedical Genetics Univeristy of Rochester, Rochester, NY, USA

    Y Sun, D Gao & Y Liu

  2. Department of Pathology, School of Medicine and Dentistry, University of Rochester, Rochester, NY, USA

    J Huang

  3. Huntsman Cancer Institute, Salt Lake City, UT, USA

    S Lessnick

  4. Laboratory of Molecular & Cellular Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan

    S Tanaka

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Correspondence to Y Sun.

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Sun, Y., Gao, D., Liu, Y. et al. IGF2 is critical for tumorigenesis by synovial sarcoma oncoprotein SYT-SSX1. Oncogene 25, 1042–1052 (2006). https://doi.org/10.1038/sj.onc.1209143

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