A1 Refereed original research article in a scientific journal
Frizzled-8 integrates Wnt-11 and transforming growth factor-beta signaling in prostate cancer
Authors: Murillo-Garzon V, Gorrono-Etxebarria I, Akerfelt M, Puustinen MC, Sistonen L, Nees M, Carton J, Waxman J, Kypta RM
Publisher: NATURE PUBLISHING GROUP
Publication year: 2018
Journal: Nature Communications
Journal name in source: NATURE COMMUNICATIONS
Journal acronym: NAT COMMUN
Article number: ARTN 1747
Volume: 9
Number of pages: 16
ISSN: 2041-1723
DOI: https://doi.org/10.1038/s41467-018-04042-w
Self-archived copy’s web address: https://research.utu.fi/converis/portal/Publication/31606100
Wnt-11 promotes cancer cell migration and invasion independently of beta-catenin but the receptors involved remain unknown. Here, we provide evidence that FZD(8) is a major Wnt-11 receptor in prostate cancer that integrates Wnt-11 and TGF-beta signals to promote EMT. FZD(8) 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 FZD(8) in cancer, correlating with Wnt-11. FZD(8) co-localizes and co-immunoprecipitates with Wnt-11 and potentiates Wnt-11 activation of ATF2-dependent transcription. FZD(8) silencing reduces prostate cancer cell migration, invasion, three-dimensional (3D) organotypic cell growth, expression of EMT-related genes, and TGF-beta/Smad-dependent signaling. Mechanistically, FZD(8) forms a TGF-beta-regulated complex with TGF-beta receptors that is mediated by the extracellular domains of FZD(8) and TGFBR1. Targeting FZD(8) may therefore inhibit aberrant activation of both Wnt and TGF-beta signals in prostate cancer.
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