Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Regan, JL; Schumacher, D; Staudte, S; Steffen, A; Haybaeck, J; Keilholz, U; Schweiger, C; Golob-Schwarzl, N; Mumberg, D; Henderson, D; Lehrach, H; Regenbrecht, CRA; Schäfer, R; Lange, M.
Non-Canonical Hedgehog Signaling Is a Positive Regulator of the WNT Pathway and Is Required for the Survival of Colon Cancer Stem Cells.
Cell Rep. 2017; 21(10):2813-2828
Doi: 10.1016/j.celrep.2017.11.025
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- Co-authors Med Uni Graz
- Golob-Schwarzl Nicole
- Haybäck Johannes
- Schweiger Caroline
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- 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. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Colonic Neoplasms - metabolism
- Female -
- Hedgehog Proteins - metabolism
- Humans -
- Mice -
- Mice, Nude -
- Neoplastic Stem Cells - metabolism
- Patched-1 Receptor - genetics
- Patched-1 Receptor - metabolism
- Wnt Signaling Pathway - physiology