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GLI1-dependent transcriptional repression of CYLD in basal cell carcinoma

Oncogene volume 30, pages 4523–4530 (2011)Cite this article

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Abstract

CYLD is a deubiquitination enzyme that regulates different cellular processes, such as cell proliferation and cell survival. Mutation and loss of heterozygosity of the CYLD gene causes development of cylindromatosis, a benign tumour originating from the skin. Our study shows that CYLD expression is dramatically downregulated in basal cell carcinoma (BCC), the most common cancer in humans. Reduced CYLD expression in basal cell carcinoma was mediated by GLI1-dependent activation of the transcriptional repressor Snail. Inhibition of GLI1 restored the CYLD expression-mediated Snail signaling pathway, and caused a significant delay in the G1 to S phase transition, as well as proliferation. Our data suggest that GLI1-mediated suppression of CYLD has a significant role in basal cell carcinoma progression.

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Acknowledgements

We thank Rudolf Jung and Elise Nilsson for excellent technical assistance, Dr Anders Edsjö, for discussion, Dr Ervin H Epstein for the mouse BCC cell line ASZ001 and CSZ-1. This work was supported by the Swedish Society for Medical Research, Swedish Cancer Foundation, Swedish Medical Research Council, Crafoordska Foundation, Royal Physiographic Society in Lund, Gunnar Nilsson Cancer Foundation, U-MAS Research Foundations and ERC grant to RM and the Austrian Science Fund FWF (projects P20652), the priority program of the University of Salzburg and the Austrian Genome program Gen-AU to FA.

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Authors and Affiliations

  1. Institute of Pathology, University of Regensburg, Regensburg, Germany

    S Kuphal & A K Bosserhoff

  2. Department of Laboratory Medicine, Lund University, UMAS, Malmö, Sweden

    G Shaw-Hallgren & R Massoumi

  3. Department of Molecular Biology, University of Salzburg, Salzburg, Austria

    M Eberl & F Aberger

  4. Department of Dermatology, University of Regensburg, Regensburg, Germany

    S Karrer

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  1. S Kuphal
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  2. G Shaw-Hallgren
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  3. M Eberl
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  4. S Karrer
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  5. F Aberger
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  6. A K Bosserhoff
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  7. R Massoumi
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Correspondence to R Massoumi.

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Kuphal, S., Shaw-Hallgren, G., Eberl, M. et al. GLI1-dependent transcriptional repression of CYLD in basal cell carcinoma. Oncogene 30, 4523–4530 (2011). https://doi.org/10.1038/onc.2011.163

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