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Activation of β-catenin/TCF targets following loss of the tumor suppressor SNF5

Oncogene volume 33, pages 933–938 (2014)Cite this article

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Abstract

The SWI/SNF chromatin remodeling complex is a master regulator of developmental cell-fate decisions, although the key target pathways are poorly characterized. Here, we interrogated the contribution of the SWI/SNF subunit and tumor suppressor SNF5 to the regulation of developmental pathways using conditional mouse and cell culture models. We find that loss of SNF5 phenocopies β-catenin hyperactivation and that SNF5 is essential for regulating Wnt/β-catenin pathway target expression. These data provide insight into chromatin-based mechanisms that underlie developmental regulation and elucidate the emerging theme that mutation of this tumor suppressor complex can activate developmental pathways by uncoupling them from upstream control.

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Acknowledgements

We thank ES McKenna for critical reading of the manuscript and A Lassar for helpful discussions. The in situ probe constructs were generously provided by C Tabin (Harvard Medical School). This work was supported in part by National Cancer Institute, National Institutes of Health Pre-Doctoral NRSA award 1F31CA130553 (ELMB), R01CA113794 (CWMR) and U01-1156106 (Stuart H Orkin). CWM R is a recipient of a Stand Up 2 Cancer Innovative Research Grant. Miles for Mary, The Garrett B Smith Foundation and Cure AT/RT Now provided additional support.

Author contributions: E.L.M-B initiated the studies, conducted experiments, analyzed data and contributed to writing the manuscript. Y.M., E.J.T, Y-J.C. and C.S.T conducted experiments and analyzed data. S.L.P and W.S. supervised portions of the studies and assisted in the data analysis. C.W.M.R supervised the studies, assisted in the data analysis and contributed to the writing of the manuscript.

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Author notes

  1. E L Mora-Blanco

    Present address: 5Current Address: Department of Cancer and DNA Damage Responses, Lawrence Berkeley National Lab, Berkeley, CA 94720, USA,

  2. Y-J Cho

    Present address: 6Current Address: Department of Neurology & Neurological Sciences, Stanford Medical School, Stanford, CA 94305, USA,

  3. C S Thom

    Present address: 7Current Address: Cell and Molecular Biology Graduate Group, University of Pennsylvania School of Medicine, Philadelphia, PA 19146, USA,

Authors and Affiliations

  1. Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA, USA

    E L Mora-Blanco, E J Tillman, C S Thom & C W M Roberts

  2. Division of Hematology/Oncology, Department of Pediatrics, Children’s Hospital Boston, Harvard Medical School, Boston, MA, USA

    E L Mora-Blanco, E J Tillman, C S Thom & C W M Roberts

  3. Novartis Institute For Biomedical Research, Cambridge, MA, USA

    Y Mishina & W Shao

  4. Department of Neurology, Children’s Hospital Boston, Boston, MA, USA

    Y-J Cho & S L Pomeroy

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  1. E L Mora-Blanco
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Correspondence to C W M Roberts.

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Mora-Blanco, E., Mishina, Y., Tillman, E. et al. Activation of β-catenin/TCF targets following loss of the tumor suppressor SNF5. Oncogene 33, 933–938 (2014). https://doi.org/10.1038/onc.2013.37

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  • DOI: https://doi.org/10.1038/onc.2013.37

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