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The synovial sarcoma translocation protein SYT-SSX2 recruits β-catenin to the nucleus and associates with it in an active complex

Oncogene volume 25, pages 3661–3669 (2006)Cite this article

Abstract

Localization of β-catenin in the cell is a key determinant in its decision to function as a critical mediator of cell adhesion at the surface or a transcription activator in the nucleus. SYT-SSX2 is the fusion product of the chromosomal translocation, t(X;18)(p11.2;q11.2), which occurs in synovial sarcoma, a soft tissue tumor. SYT-SSX2 is known to associate with chromatin remodeling complexes and is proposed to be involved in controlling gene expression. We report that SYT-SSX2 plays a direct role in β-catenin regulation. When expressed in mammalian cells, SYT-SSX2-induced β-catenin recruitment to the nucleus. Interestingly, known target genes of canonical Wnt were not activated as a result of SYT-SSX2 expression, nor was the nuclear localization of β-catenin due to one of the signaling pathways normally implicated in this event. β-Catenin accumulation in the nucleus led to the formation of a transcriptionally active nuclear complex that contained SYT-SSX2 and β-catenin. More importantly, depletion of SYT-SSX2 in primary synovial sarcoma cells resulted in loss of nuclear β-catenin signal and a significant decrease in its signaling activity. These results unravel a novel pathway in the control of β-catenin cellular transport and strongly suggest that SYT-SSX2 contributes to tumor development, in part through β-catenin signaling.

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Acknowledgements

We thank Kelli Gunn and the Al Reynolds group for technical support, Pat Nakatani for the POZ retroviral vector, Hans Clevers and Bert Vogelstein for the TOP-FLASH, FOP-FLASH, MYC-and wt-β-catenin constructs, Jonathan Fletcher for the Syn-1 cells, Ray Mernaugh for help with peptide design and Open Biosystems for the SSX2 antibody. This work was supported by Grants K22 CA098008-01 and R01CA106481-01, and in part by a Cancer Center Support Grant CA68485 and Center in Molecular Toxicology Support Grant EB00672. Some of the work began in David Livingston's laboratory (Dana Farber Cancer Institute) and was supported by Grant NCI CA 15751.

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  1. Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN, USA

    D Pretto, R Barco, J Rivera, N Neel, M D Gustavson & J E Eid

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  1. D Pretto
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Correspondence to J E Eid.

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Pretto, D., Barco, R., Rivera, J. et al. The synovial sarcoma translocation protein SYT-SSX2 recruits β-catenin to the nucleus and associates with it in an active complex. Oncogene 25, 3661–3669 (2006). https://doi.org/10.1038/sj.onc.1209413

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