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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.
- Source :
- Cell Reports; 12/5/2017, Vol. 21 Issue 10, preceding p2813-2828, 17p
- Publication Year :
- 2017
-
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, noncanonical 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 26391856
- Volume :
- 21
- Issue :
- 10
- Database :
- Complementary Index
- Journal :
- Cell Reports
- Publication Type :
- Academic Journal
- Accession number :
- 126596315
- Full Text :
- https://doi.org/10.1016/j.celrep.2017.11.025