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PKCζ facilitates lymphatic metastatic spread of prostate cancer cells in a mice xenograft model
Prostate cancer disseminates primarily into the adjacent lymph nodes, which is related to a poor outcome. Atypical protein kinase C ζ (PKCζ) is highly expressed in aggressive prostate cancer and correlates with Gleason score, clinical stage, and poor prognosis. Here, we report the molecular mechanis...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756056/ https://www.ncbi.nlm.nih.gov/pubmed/30705401 http://dx.doi.org/10.1038/s41388-019-0722-9 |
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author | Zang, Guangxiang Mu, Yabing Gao, Linlin Bergh, Anders Landström, Marene |
author_facet | Zang, Guangxiang Mu, Yabing Gao, Linlin Bergh, Anders Landström, Marene |
author_sort | Zang, Guangxiang |
collection | PubMed |
description | Prostate cancer disseminates primarily into the adjacent lymph nodes, which is related to a poor outcome. Atypical protein kinase C ζ (PKCζ) is highly expressed in aggressive prostate cancer and correlates with Gleason score, clinical stage, and poor prognosis. Here, we report the molecular mechanisms of PKCζ in lymphatic metastasis during prostate cancer progression. Using zinc-finger nuclease technology or PKCζ shRNA lentiviral particles, and orthotopic mouse xenografts, we show that PKCζ-knockout or knockdown from aggressive prostate cancer (PC3 and PC3U) cells, decreasesd tumor growth and lymphatic metastasis in vivo. Intriguingly, PKCζ-knockout or knockdown impaired the activation of AKT, ERK, and NF-κB signaling in prostate cancer cells, thereby impairing the expression of lymphangiogenic factors and macrophage recruitment, resulting in aberrant lymphangiogenesis. Moreover, PKCζ regulated the expression of hyaluronan synthase enzymes, which is important for hyaluronan-mediated lymphatic drainage and tumor dissemination. Thus, PKCζ plays a crucial oncogenic role in the lymphatic metastasis of prostate cancer and is predicted to be a novel therapeutic target for prostate cancer. |
format | Online Article Text |
id | pubmed-6756056 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-67560562019-09-24 PKCζ facilitates lymphatic metastatic spread of prostate cancer cells in a mice xenograft model Zang, Guangxiang Mu, Yabing Gao, Linlin Bergh, Anders Landström, Marene Oncogene Article Prostate cancer disseminates primarily into the adjacent lymph nodes, which is related to a poor outcome. Atypical protein kinase C ζ (PKCζ) is highly expressed in aggressive prostate cancer and correlates with Gleason score, clinical stage, and poor prognosis. Here, we report the molecular mechanisms of PKCζ in lymphatic metastasis during prostate cancer progression. Using zinc-finger nuclease technology or PKCζ shRNA lentiviral particles, and orthotopic mouse xenografts, we show that PKCζ-knockout or knockdown from aggressive prostate cancer (PC3 and PC3U) cells, decreasesd tumor growth and lymphatic metastasis in vivo. Intriguingly, PKCζ-knockout or knockdown impaired the activation of AKT, ERK, and NF-κB signaling in prostate cancer cells, thereby impairing the expression of lymphangiogenic factors and macrophage recruitment, resulting in aberrant lymphangiogenesis. Moreover, PKCζ regulated the expression of hyaluronan synthase enzymes, which is important for hyaluronan-mediated lymphatic drainage and tumor dissemination. Thus, PKCζ plays a crucial oncogenic role in the lymphatic metastasis of prostate cancer and is predicted to be a novel therapeutic target for prostate cancer. Nature Publishing Group UK 2019-01-31 2019 /pmc/articles/PMC6756056/ /pubmed/30705401 http://dx.doi.org/10.1038/s41388-019-0722-9 Text en © The Author(s) 2019 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 Zang, Guangxiang Mu, Yabing Gao, Linlin Bergh, Anders Landström, Marene PKCζ facilitates lymphatic metastatic spread of prostate cancer cells in a mice xenograft model |
title | PKCζ facilitates lymphatic metastatic spread of prostate cancer cells in a mice xenograft model |
title_full | PKCζ facilitates lymphatic metastatic spread of prostate cancer cells in a mice xenograft model |
title_fullStr | PKCζ facilitates lymphatic metastatic spread of prostate cancer cells in a mice xenograft model |
title_full_unstemmed | PKCζ facilitates lymphatic metastatic spread of prostate cancer cells in a mice xenograft model |
title_short | PKCζ facilitates lymphatic metastatic spread of prostate cancer cells in a mice xenograft model |
title_sort | pkcζ facilitates lymphatic metastatic spread of prostate cancer cells in a mice xenograft model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6756056/ https://www.ncbi.nlm.nih.gov/pubmed/30705401 http://dx.doi.org/10.1038/s41388-019-0722-9 |
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