β-catenin-independent regulation of Wnt target genes by RoR2 and ATF2/ATF4 in colon cancer cells
Wnt signaling is an evolutionarily conserved signaling route required for development and homeostasis. While canonical, β-catenin-dependent Wnt signaling is well studied and has been linked to many forms of cancer, much less is known about the role of non-canonical, β-catenin-independent Wnt signali...
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| Main Authors: | , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
16 February 2018
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| In: |
Scientific reports
Year: 2018, Volume: 8 |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-018-20641-5 |
| Online Access: | Verlag, Volltext: https://doi.org/10.1038/s41598-018-20641-5 Verlag, Volltext: https://www.nature.com/articles/s41598-018-20641-5 
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| Author Notes: | Oksana Voloshanenko, Uwe Schwartz, Dominique Kranz, Benedikt Rauscher, Michael Linnebacher, Iris Augustin, Michael Boutros |
| Summary: | Wnt signaling is an evolutionarily conserved signaling route required for development and homeostasis. While canonical, β-catenin-dependent Wnt signaling is well studied and has been linked to many forms of cancer, much less is known about the role of non-canonical, β-catenin-independent Wnt signaling. Here, we aimed at identifying a β-catenin-independent Wnt target gene signature in order to understand the functional significance of non-canonical signaling in colon cancer cells. Gene expression profiling was performed after silencing of key components of Wnt signaling pathway and an iterative signature algorithm was applied to predict pathway-dependent gene signatures. Independent experiments confirmed several target genes, including PLOD2, HADH, LCOR and REEP1 as non-canonical target genes in various colon cancer cells. Moreover, non-canonical Wnt target genes are regulated via RoR2, Dvl2, ATF2 and ATF4. Furthermore, we show that the ligands Wnt5a/b are upstream regulators of the non-canonical signature and moreover regulate proliferation of cancer cells in a β-catenin-independent manner. Our experiments indicate that colon cancer cells are dependent on both β-catenin-dependent and -independent Wnt signaling routes for growth and proliferation. |
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| Item Description: | Gesehen am 29.03.2019 |
| Physical Description: | Online Resource |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/s41598-018-20641-5 |