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  Non-Canonical Hedgehog Signaling Is a Positive Regulator of the WNT Pathway and Is Required for the Survival of Colon Cancer Stem Cells

Regan, J. L., Schumacher, D., Staudte, S., Steffen, A., Haybaeck, J., Keilholz, U., et al. (2017). Non-Canonical Hedgehog Signaling Is a Positive Regulator of the WNT Pathway and Is Required for the Survival of Colon Cancer Stem Cells. Cell Reports, 21(10), 2813-2828. doi:10.1016/j.celrep.2017.11.025.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0000-F693-4 Version Permalink: http://hdl.handle.net/21.11116/0000-0000-F694-3
Genre: Journal Article

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 Creators:
Regan, J. L., Author
Schumacher, D., Author
Staudte, S., Author
Steffen, A., Author
Haybaeck, J., Author
Keilholz, U., Author
Schweiger, C., Author
Golob-Schwarzl, N., Author
Mumberg, D., Author
Henderson, D., Author
Lehrach, H.1, Author              
Regenbrecht, C. R. A., Author
Schafer, R., Author
Lange, M., Author
Affiliations:
1Emeritus Group of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_2385697              

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Free keywords: Hhat Ptch1 Shh WNT pathway cancer organoid cancer stem cell colon cancer non-canonical Hedgehog signaling
 Abstract: Colon cancer is a heterogeneous tumor driven by a subpopulation of cancer stem cells (CSCs). To study CSCs in colon cancer, we used limiting dilution spheroid and serial xenotransplantation assays to functionally define the frequency of CSCs in a panel of patient-derived cancer organoids. These studies demonstrated cancer organoids to be enriched for CSCs, which varied in frequency between tumors. Whole-transcriptome analysis identified WNT and Hedgehog signaling components to be enhanced in CSC-enriched tumors and in aldehyde dehydrogenase (ALDH)-positive CSCs. Canonical GLI-dependent Hedgehog signaling is a negative regulator of WNT signaling in normal intestine and intestinal tumors. Here, we show that Hedgehog signaling in colon CSCs is autocrine SHH-dependent, non-canonical PTCH1 dependent, and GLI independent. In addition, using small-molecule inhibitors and RNAi against SHH-palmitoylating Hedgehog acyltransferase (HHAT), we demonstrate that non-canonical Hedgehog signaling is a positive regulator of WNT signaling and required for colon CSC survival.

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Language(s): eng - English
 Dates: 2017-11-062017-12-05
 Publication Status: Published online
 Pages: 16
 Publishing info: -
 Table of Contents: -
 Rev. Method: -
 Identifiers: DOI: 10.1016/j.celrep.2017.11.025
ISSN: 2211-1247 (Electronic)
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Title: Cell Reports
Source Genre: Journal
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Publ. Info: Maryland Heights, MO : Cell Press
Pages: - Volume / Issue: 21 (10) Sequence Number: - Start / End Page: 2813 - 2828 Identifier: ISSN: 2211-1247
CoNE: /journals/resource/2211-1247