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WFDC2 suppresses prostate cancer metastasis by modulating EGFR signaling inactivation

WAP four-disulfide core domain 2 (WFDC2) is a small secretory protein that has been widely studied in ovarian cancer. It has been proven that WFDC2 promotes proliferation and metastasis in ovarian cancer, and serves as a diagnostic biomarker. However, the specific function of WFDC2 in prostate cance...

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Autores principales: Xiong, Yaoyi, Yuan, Lushun, Chen, Song, Xu, Huimin, Peng, Tianchen, Ju, Lingao, Wang, Gang, Xiao, Yu, Wang, Xinghuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366654/
https://www.ncbi.nlm.nih.gov/pubmed/32678075
http://dx.doi.org/10.1038/s41419-020-02752-y
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author Xiong, Yaoyi
Yuan, Lushun
Chen, Song
Xu, Huimin
Peng, Tianchen
Ju, Lingao
Wang, Gang
Xiao, Yu
Wang, Xinghuan
author_facet Xiong, Yaoyi
Yuan, Lushun
Chen, Song
Xu, Huimin
Peng, Tianchen
Ju, Lingao
Wang, Gang
Xiao, Yu
Wang, Xinghuan
author_sort Xiong, Yaoyi
collection PubMed
description WAP four-disulfide core domain 2 (WFDC2) is a small secretory protein that has been widely studied in ovarian cancer. It has been proven that WFDC2 promotes proliferation and metastasis in ovarian cancer, and serves as a diagnostic biomarker. However, the specific function of WFDC2 in prostate cancer has not been reported. Here, we first screened the diagnostic marker and favorable prognostic factor WFDC2 in prostate cancer by bioinformatics. WFDC2 expression was negatively correlated with Gleason score and metastasis in prostate cancer. Then, we revealed that overexpression of WFDC2, and addition of recombinant protein HE4 can significantly inhibit prostate cancer metastasis in vivo and in vitro. By co-immunoprecipitation and co-localization assays, we proved that WFDC2 binds to the extracellular domain of epidermal growth factor receptor (EGFR). Immunoblot showed that WFDC2 overexpression and recombinant protein HE4 addition inactivated the EGFR/AKT/GSK3B/Snail signaling pathway, and then restrained the progression of epithelial–mesenchymal transition. In conclusion, our study identified that the tumor suppressor WFDC2 can suppress prostate cancer metastasis by inactivating EGFR signaling.
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spelling pubmed-73666542020-07-21 WFDC2 suppresses prostate cancer metastasis by modulating EGFR signaling inactivation Xiong, Yaoyi Yuan, Lushun Chen, Song Xu, Huimin Peng, Tianchen Ju, Lingao Wang, Gang Xiao, Yu Wang, Xinghuan Cell Death Dis Article WAP four-disulfide core domain 2 (WFDC2) is a small secretory protein that has been widely studied in ovarian cancer. It has been proven that WFDC2 promotes proliferation and metastasis in ovarian cancer, and serves as a diagnostic biomarker. However, the specific function of WFDC2 in prostate cancer has not been reported. Here, we first screened the diagnostic marker and favorable prognostic factor WFDC2 in prostate cancer by bioinformatics. WFDC2 expression was negatively correlated with Gleason score and metastasis in prostate cancer. Then, we revealed that overexpression of WFDC2, and addition of recombinant protein HE4 can significantly inhibit prostate cancer metastasis in vivo and in vitro. By co-immunoprecipitation and co-localization assays, we proved that WFDC2 binds to the extracellular domain of epidermal growth factor receptor (EGFR). Immunoblot showed that WFDC2 overexpression and recombinant protein HE4 addition inactivated the EGFR/AKT/GSK3B/Snail signaling pathway, and then restrained the progression of epithelial–mesenchymal transition. In conclusion, our study identified that the tumor suppressor WFDC2 can suppress prostate cancer metastasis by inactivating EGFR signaling. Nature Publishing Group UK 2020-07-16 /pmc/articles/PMC7366654/ /pubmed/32678075 http://dx.doi.org/10.1038/s41419-020-02752-y Text en © The Author(s) 2020 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
Xiong, Yaoyi
Yuan, Lushun
Chen, Song
Xu, Huimin
Peng, Tianchen
Ju, Lingao
Wang, Gang
Xiao, Yu
Wang, Xinghuan
WFDC2 suppresses prostate cancer metastasis by modulating EGFR signaling inactivation
title WFDC2 suppresses prostate cancer metastasis by modulating EGFR signaling inactivation
title_full WFDC2 suppresses prostate cancer metastasis by modulating EGFR signaling inactivation
title_fullStr WFDC2 suppresses prostate cancer metastasis by modulating EGFR signaling inactivation
title_full_unstemmed WFDC2 suppresses prostate cancer metastasis by modulating EGFR signaling inactivation
title_short WFDC2 suppresses prostate cancer metastasis by modulating EGFR signaling inactivation
title_sort wfdc2 suppresses prostate cancer metastasis by modulating egfr signaling inactivation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366654/
https://www.ncbi.nlm.nih.gov/pubmed/32678075
http://dx.doi.org/10.1038/s41419-020-02752-y
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