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GIPC2 interacts with Fzd7 to promote prostate cancer metastasis by activating WNT signaling
Prostate cancer (PCa) causes significant mortality and morbidity, with advanced metastasis. WNT signaling is a promising therapeutic target for metastatic PCa. GIPC2 is a GIPC1 paralog involved in WNT signaling pathways associated with tumor progression, but its role in PCa metastasis remains unclea...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9054671/ https://www.ncbi.nlm.nih.gov/pubmed/35347223 http://dx.doi.org/10.1038/s41388-022-02255-4 |
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author | Wang, Liang Wang, Jiayi Yin, Xiaolin Guan, Xin Li, Ying Xin, Chenqi Liu, Jing |
author_facet | Wang, Liang Wang, Jiayi Yin, Xiaolin Guan, Xin Li, Ying Xin, Chenqi Liu, Jing |
author_sort | Wang, Liang |
collection | PubMed |
description | Prostate cancer (PCa) causes significant mortality and morbidity, with advanced metastasis. WNT signaling is a promising therapeutic target for metastatic PCa. GIPC2 is a GIPC1 paralog involved in WNT signaling pathways associated with tumor progression, but its role in PCa metastasis remains unclear. Herein, we demonstrated that high GIPC2 expression in PCa tissues was significantly associated with distant metastasis and poor prognosis. Functional studies demonstrated that high GIPC2 expression due to CpG-island demethylation promoted increased metastatic capabilities of PCa cells. Conversely, silencing GIPC2 expression significantly inhibited PCa metastasis in vitro and in vivo. Furthermore, GIPC2 directly bound the WNT co-receptor Fzd7 through its PDZ domain, which enabled activation of WNT-β-catenin cascades, thereby stimulating PCa metastasis. Interestingly, GIPC2 protein was also identified as a component of exosomes and that it robustly stimulated PCa adhesion, invasion, and migration. The presence of GIPC2 in tumor-derived exosomes and ability to impact the behavior of tumor cells suggest that GIPC2 is a novel epigenetic oncogene involved in PCa metastasis. Our findings identified GIPC2 as a novel exosomal molecule associated with WNT signaling and may represent a potential therapeutic target and biomarker for metastatic PCa. |
format | Online Article Text |
id | pubmed-9054671 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-90546712022-05-01 GIPC2 interacts with Fzd7 to promote prostate cancer metastasis by activating WNT signaling Wang, Liang Wang, Jiayi Yin, Xiaolin Guan, Xin Li, Ying Xin, Chenqi Liu, Jing Oncogene Article Prostate cancer (PCa) causes significant mortality and morbidity, with advanced metastasis. WNT signaling is a promising therapeutic target for metastatic PCa. GIPC2 is a GIPC1 paralog involved in WNT signaling pathways associated with tumor progression, but its role in PCa metastasis remains unclear. Herein, we demonstrated that high GIPC2 expression in PCa tissues was significantly associated with distant metastasis and poor prognosis. Functional studies demonstrated that high GIPC2 expression due to CpG-island demethylation promoted increased metastatic capabilities of PCa cells. Conversely, silencing GIPC2 expression significantly inhibited PCa metastasis in vitro and in vivo. Furthermore, GIPC2 directly bound the WNT co-receptor Fzd7 through its PDZ domain, which enabled activation of WNT-β-catenin cascades, thereby stimulating PCa metastasis. Interestingly, GIPC2 protein was also identified as a component of exosomes and that it robustly stimulated PCa adhesion, invasion, and migration. The presence of GIPC2 in tumor-derived exosomes and ability to impact the behavior of tumor cells suggest that GIPC2 is a novel epigenetic oncogene involved in PCa metastasis. Our findings identified GIPC2 as a novel exosomal molecule associated with WNT signaling and may represent a potential therapeutic target and biomarker for metastatic PCa. Nature Publishing Group UK 2022-03-28 2022 /pmc/articles/PMC9054671/ /pubmed/35347223 http://dx.doi.org/10.1038/s41388-022-02255-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/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/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Wang, Liang Wang, Jiayi Yin, Xiaolin Guan, Xin Li, Ying Xin, Chenqi Liu, Jing GIPC2 interacts with Fzd7 to promote prostate cancer metastasis by activating WNT signaling |
title | GIPC2 interacts with Fzd7 to promote prostate cancer metastasis by activating WNT signaling |
title_full | GIPC2 interacts with Fzd7 to promote prostate cancer metastasis by activating WNT signaling |
title_fullStr | GIPC2 interacts with Fzd7 to promote prostate cancer metastasis by activating WNT signaling |
title_full_unstemmed | GIPC2 interacts with Fzd7 to promote prostate cancer metastasis by activating WNT signaling |
title_short | GIPC2 interacts with Fzd7 to promote prostate cancer metastasis by activating WNT signaling |
title_sort | gipc2 interacts with fzd7 to promote prostate cancer metastasis by activating wnt signaling |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9054671/ https://www.ncbi.nlm.nih.gov/pubmed/35347223 http://dx.doi.org/10.1038/s41388-022-02255-4 |
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