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NDRG3 lowers the metastatic potential in prostate cancer as a feedback controller of hypoxia-inducible factors
Expression of hypoxia-inducible factors (HIFs) and N-myc downstream-regulated gene 3 (NDRG3) are oxygen-dependently regulated by prolyl hydroxylase domain (PHD) enzymes. Little is known about the role of NDRG3 in the cellular adaptation to hypoxia, whereas the roles of HIFs are well understood. In t...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5951909/ https://www.ncbi.nlm.nih.gov/pubmed/29760417 http://dx.doi.org/10.1038/s12276-018-0089-y |
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author | Lee, Ga Young Shin, Seung-Hyun Shin, Hyun-Woo Chun, Yang-Sook Park, Jong-Wan |
author_facet | Lee, Ga Young Shin, Seung-Hyun Shin, Hyun-Woo Chun, Yang-Sook Park, Jong-Wan |
author_sort | Lee, Ga Young |
collection | PubMed |
description | Expression of hypoxia-inducible factors (HIFs) and N-myc downstream-regulated gene 3 (NDRG3) are oxygen-dependently regulated by prolyl hydroxylase domain (PHD) enzymes. Little is known about the role of NDRG3 in the cellular adaptation to hypoxia, whereas the roles of HIFs are well understood. In this study, we investigated how NDRG3 affects the hypoxic response in prostate cancer cells. Compared with HIF-1α, hypoxic induction of NDRG3 was observed at a later phase. NDRG3 reduced hypoxic expression of HIF-1α by inhibiting AKT-driven translation of HIF1A mRNA. In addition, NDRG3 functionally inhibited HIF-1 by dissociating the coactivator p300 from HIF-1α. Accordingly, NDRG3 may fine-tune the HIF-1 signaling pathway to cope with long-term hypoxia. Of the diverse effects of HIF-1α on cancer progression, hypoxia-induced cell migration was investigated. In transwell chambers, NDRG3 negatively regulated the migration and invasion of prostate cancer cells under hypoxia. An informatics analysis using Gene Expression Omnibus (GEO) revealed that NDRG3 downregulation is associated with prostate cancer metastasis and high expression of HIF-1 downstream genes. In cancer tissue arrays, NDRG3 expression was lower in prostate cancer tissues with a Gleason score of 8 or greater and was inversely correlated with HIF-1α expression. Therefore, NDRG3 may have an anti-metastatic function in prostate cancer under a hypoxic microenvironment. |
format | Online Article Text |
id | pubmed-5951909 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-59519092018-05-15 NDRG3 lowers the metastatic potential in prostate cancer as a feedback controller of hypoxia-inducible factors Lee, Ga Young Shin, Seung-Hyun Shin, Hyun-Woo Chun, Yang-Sook Park, Jong-Wan Exp Mol Med Article Expression of hypoxia-inducible factors (HIFs) and N-myc downstream-regulated gene 3 (NDRG3) are oxygen-dependently regulated by prolyl hydroxylase domain (PHD) enzymes. Little is known about the role of NDRG3 in the cellular adaptation to hypoxia, whereas the roles of HIFs are well understood. In this study, we investigated how NDRG3 affects the hypoxic response in prostate cancer cells. Compared with HIF-1α, hypoxic induction of NDRG3 was observed at a later phase. NDRG3 reduced hypoxic expression of HIF-1α by inhibiting AKT-driven translation of HIF1A mRNA. In addition, NDRG3 functionally inhibited HIF-1 by dissociating the coactivator p300 from HIF-1α. Accordingly, NDRG3 may fine-tune the HIF-1 signaling pathway to cope with long-term hypoxia. Of the diverse effects of HIF-1α on cancer progression, hypoxia-induced cell migration was investigated. In transwell chambers, NDRG3 negatively regulated the migration and invasion of prostate cancer cells under hypoxia. An informatics analysis using Gene Expression Omnibus (GEO) revealed that NDRG3 downregulation is associated with prostate cancer metastasis and high expression of HIF-1 downstream genes. In cancer tissue arrays, NDRG3 expression was lower in prostate cancer tissues with a Gleason score of 8 or greater and was inversely correlated with HIF-1α expression. Therefore, NDRG3 may have an anti-metastatic function in prostate cancer under a hypoxic microenvironment. Nature Publishing Group UK 2018-05-14 /pmc/articles/PMC5951909/ /pubmed/29760417 http://dx.doi.org/10.1038/s12276-018-0089-y Text en © The Author(s) 2018 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, and provide a link to the Creative Commons license. You do not have permission under this license to share adapted material derived from this article or parts of it. 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-nc-nd/4.0/. |
spellingShingle | Article Lee, Ga Young Shin, Seung-Hyun Shin, Hyun-Woo Chun, Yang-Sook Park, Jong-Wan NDRG3 lowers the metastatic potential in prostate cancer as a feedback controller of hypoxia-inducible factors |
title | NDRG3 lowers the metastatic potential in prostate cancer as a feedback controller of hypoxia-inducible factors |
title_full | NDRG3 lowers the metastatic potential in prostate cancer as a feedback controller of hypoxia-inducible factors |
title_fullStr | NDRG3 lowers the metastatic potential in prostate cancer as a feedback controller of hypoxia-inducible factors |
title_full_unstemmed | NDRG3 lowers the metastatic potential in prostate cancer as a feedback controller of hypoxia-inducible factors |
title_short | NDRG3 lowers the metastatic potential in prostate cancer as a feedback controller of hypoxia-inducible factors |
title_sort | ndrg3 lowers the metastatic potential in prostate cancer as a feedback controller of hypoxia-inducible factors |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5951909/ https://www.ncbi.nlm.nih.gov/pubmed/29760417 http://dx.doi.org/10.1038/s12276-018-0089-y |
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