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Luteolin attenuates Wnt signaling via upregulation of FZD6 to suppress prostate cancer stemness revealed by comparative proteomics

The mechanisms underlying luteolin-induced inhibition of prostate cancer (PCa) stemness have remained elusive. Here, we report that luteolin suppresses PCa stemness through Wnt signaling by upregulation of FZD6 (frizzled class receptor 6). Luteolin inhibits PCa cell proliferation, migration, self-re...

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Autores principales: Han, Kun, Lang, Tingyuan, Zhang, Zhiqi, Zhang, Yi, Sun, Yongning, Shen, Zan, Beuerman, Roger W., Zhou, Lei, Min, Daliu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986741/
https://www.ncbi.nlm.nih.gov/pubmed/29867083
http://dx.doi.org/10.1038/s41598-018-26761-2
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author Han, Kun
Lang, Tingyuan
Zhang, Zhiqi
Zhang, Yi
Sun, Yongning
Shen, Zan
Beuerman, Roger W.
Zhou, Lei
Min, Daliu
author_facet Han, Kun
Lang, Tingyuan
Zhang, Zhiqi
Zhang, Yi
Sun, Yongning
Shen, Zan
Beuerman, Roger W.
Zhou, Lei
Min, Daliu
author_sort Han, Kun
collection PubMed
description The mechanisms underlying luteolin-induced inhibition of prostate cancer (PCa) stemness have remained elusive. Here, we report that luteolin suppresses PCa stemness through Wnt signaling by upregulation of FZD6 (frizzled class receptor 6). Luteolin inhibits PCa cell proliferation, migration, self-renewal as well as the expression of prostate cancer stem cell markers in vitro. Through iTRAQ-based quantitative proteomics study, we identified 208 differentially expressed proteins in luteolin-treated PC-3 cells. Subsequent mechanistic analysis revealed that luteolin inhibits Wnt signaling by transcriptional upregulation of FZD6, and thereby suppressing the stemness of PCa cells. Furthermore, we identified FZD6 as a tumor suppressor that can abolish PCa stemness. In summary, our findings demonstrate that suppression of Wnt signaling by upregulation of FZD6 is a mechanism underlying luteolin-induced inhibition of PCa stemness. Our work suggests a new therapeutic strategy against human prostate cancer caused by aberrant activation of Wnt signaling.
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spelling pubmed-59867412018-06-07 Luteolin attenuates Wnt signaling via upregulation of FZD6 to suppress prostate cancer stemness revealed by comparative proteomics Han, Kun Lang, Tingyuan Zhang, Zhiqi Zhang, Yi Sun, Yongning Shen, Zan Beuerman, Roger W. Zhou, Lei Min, Daliu Sci Rep Article The mechanisms underlying luteolin-induced inhibition of prostate cancer (PCa) stemness have remained elusive. Here, we report that luteolin suppresses PCa stemness through Wnt signaling by upregulation of FZD6 (frizzled class receptor 6). Luteolin inhibits PCa cell proliferation, migration, self-renewal as well as the expression of prostate cancer stem cell markers in vitro. Through iTRAQ-based quantitative proteomics study, we identified 208 differentially expressed proteins in luteolin-treated PC-3 cells. Subsequent mechanistic analysis revealed that luteolin inhibits Wnt signaling by transcriptional upregulation of FZD6, and thereby suppressing the stemness of PCa cells. Furthermore, we identified FZD6 as a tumor suppressor that can abolish PCa stemness. In summary, our findings demonstrate that suppression of Wnt signaling by upregulation of FZD6 is a mechanism underlying luteolin-induced inhibition of PCa stemness. Our work suggests a new therapeutic strategy against human prostate cancer caused by aberrant activation of Wnt signaling. Nature Publishing Group UK 2018-06-04 /pmc/articles/PMC5986741/ /pubmed/29867083 http://dx.doi.org/10.1038/s41598-018-26761-2 Text en © The Author(s) 2018 Open Access 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/.
spellingShingle Article
Han, Kun
Lang, Tingyuan
Zhang, Zhiqi
Zhang, Yi
Sun, Yongning
Shen, Zan
Beuerman, Roger W.
Zhou, Lei
Min, Daliu
Luteolin attenuates Wnt signaling via upregulation of FZD6 to suppress prostate cancer stemness revealed by comparative proteomics
title Luteolin attenuates Wnt signaling via upregulation of FZD6 to suppress prostate cancer stemness revealed by comparative proteomics
title_full Luteolin attenuates Wnt signaling via upregulation of FZD6 to suppress prostate cancer stemness revealed by comparative proteomics
title_fullStr Luteolin attenuates Wnt signaling via upregulation of FZD6 to suppress prostate cancer stemness revealed by comparative proteomics
title_full_unstemmed Luteolin attenuates Wnt signaling via upregulation of FZD6 to suppress prostate cancer stemness revealed by comparative proteomics
title_short Luteolin attenuates Wnt signaling via upregulation of FZD6 to suppress prostate cancer stemness revealed by comparative proteomics
title_sort luteolin attenuates wnt signaling via upregulation of fzd6 to suppress prostate cancer stemness revealed by comparative proteomics
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986741/
https://www.ncbi.nlm.nih.gov/pubmed/29867083
http://dx.doi.org/10.1038/s41598-018-26761-2
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