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Phorbol esters inhibit the Hedgehog signalling pathway downstream of Suppressor of Fused, but upstream of Gli

Oncogene volume 26, pages 5163–5168 (2007)Cite this article

Abstract

The developmentally important Hedgehog (Hh) signal transduction pathway, which has recently been implicated in several forms of cancer, is subject to regulation by several protein kinases. Here, we address the role of protein kinase Cδ in pathway inhibition and show that cellular depletion or pharmacological inhibition of this kinase isoform results in a blockade of signalling between Suppressor of Fused and the Gli transcription factors. We further provide evidence that the observed pathway inhibition is independent of primary cilia and the mitogen-activated protein kinase kinase (Mek1) kinase. These findings allowed for the rapid dissection of downstream Hh pathway activation mechanisms in human tumour cells and demonstrate a surprising variation in how cells can activate signalling in a ligand- and receptor-independent manner.

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Acknowledgements

We are very grateful to Drs P Beachy, F Aberger, H Sasaki and J Bergman for kind provision of materials. This work was supported by stipends from the Wenner-Gren-Foundation, the Swedish Cancer Association and the Karolinska Institute to ML and by grants from the Swedish Cancer Association and Swiss Bridge to RT

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  1. Department of Biosciences and Nutrition, Karolinska Institutet, Novum Research Park, Huddinge, Sweden

    M Lauth, Å Bergström & R Toftgård

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  1. M Lauth
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  2. Å Bergström
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  3. R Toftgård
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Correspondence to M Lauth.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Lauth, M., Bergström, Å. & Toftgård, R. Phorbol esters inhibit the Hedgehog signalling pathway downstream of Suppressor of Fused, but upstream of Gli. Oncogene 26, 5163–5168 (2007). https://doi.org/10.1038/sj.onc.1210321

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