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Frizzled-8 integrates Wnt-11 and transforming growth factor-β signaling in prostate cancer
| File | Description | Size | Format | |
|---|---|---|---|---|
 s41467-018-04042-w.pdf | Published version | 3.28 MB | Adobe PDF | View/Open |
| Title: | Frizzled-8 integrates Wnt-11 and transforming growth factor-β signaling in prostate cancer |
| Authors: | Murillo-Garzón, V Gorroño-Etxebarria, I Åkerfelt, M Puustinen, MC Sistonen, L Nees, M Carton, J Waxman, J Kypta, RM |
| Item Type: | Journal Article |
| Abstract: | Wnt-11 promotes cancer cell migration and invasion independently of β-catenin but the receptors involved remain unknown. Here, we provide evidence that FZD8 is a major Wnt-11 receptor in prostate cancer that integrates Wnt-11 and TGF-β signals to promote EMT. FZD8 mRNA is upregulated in multiple prostate cancer datasets and in metastatic cancer cell lines in vitro and in vivo. Analysis of patient samples reveals increased levels of FZD8 in cancer, correlating with Wnt-11. FZD8 co-localizes and co-immunoprecipitates with Wnt-11 and potentiates Wnt-11 activation of ATF2-dependent transcription. FZD8 silencing reduces prostate cancer cell migration, invasion, three-dimensional (3D) organotypic cell growth, expression of EMT-related genes, and TGF-β/Smad-dependent signaling. Mechanistically, FZD8 forms a TGF-β-regulated complex with TGF-β receptors that is mediated by the extracellular domains of FZD8 and TGFBR1. Targeting FZD8 may therefore inhibit aberrant activation of both Wnt and TGF-β signals in prostate cancer. |
| Issue Date: | 1-May-2018 |
| Date of Acceptance: | 29-Mar-2018 |
| URI: | http://hdl.handle.net/10044/1/57704 |
| DOI: | https://dx.doi.org/10.1038/s41467-018-04042-w |
| ISSN: | 2041-1723 |
| Publisher: | Nature Publishing Group |
| Journal / Book Title: | Nature Communications |
| Volume: | 9 |
| Copyright Statement: | © The Author(s) 2018. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article ’ s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article ’ s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/ |
| Keywords: | Science & Technology Multidisciplinary Sciences Science & Technology - Other Topics CONVERGENT EXTENSION MOVEMENTS TGF-BETA WNT/BETA-CATENIN NONCANONICAL WNT TRANSCRIPTIONAL ACTIVATION MESENCHYMAL TRANSITION XENOPUS-LAEVIS MAJOR ROLE CELLS MECHANISMS MD Multidisciplinary |
| Publication Status: | Published |
| Open Access location: | https://rdcu.be/M402 |
| Article Number: | 1747 |
| Appears in Collections: | Department of Surgery and Cancer |