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Roles of the Na(+)/H(+) Exchanger Isoform 1 and Urokinase in Prostate Cancer Cell Migration and Invasion
Prostate cancer is a leading cause of cancer-associated deaths in men over 60 years of age. Most patients are killed by tumor metastasis. Recent evidence has implicated a role of the tumor microenvironment and urokinase plasminogen activator (uPA) in cancer cell migration, invasion, and metastasis....
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8705693/ https://www.ncbi.nlm.nih.gov/pubmed/34948058 http://dx.doi.org/10.3390/ijms222413263 |
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author | Li, Xiuju Buckley, Benjamin Stoletov, Konstantin Jing, Yang Ranson, Marie Lewis, John D. Kelso, Mike Fliegel, Larry |
author_facet | Li, Xiuju Buckley, Benjamin Stoletov, Konstantin Jing, Yang Ranson, Marie Lewis, John D. Kelso, Mike Fliegel, Larry |
author_sort | Li, Xiuju |
collection | PubMed |
description | Prostate cancer is a leading cause of cancer-associated deaths in men over 60 years of age. Most patients are killed by tumor metastasis. Recent evidence has implicated a role of the tumor microenvironment and urokinase plasminogen activator (uPA) in cancer cell migration, invasion, and metastasis. Here, we examine the role of the Na(+)/H(+) exchanger isoform 1 (NHE1) and uPA in DU 145 prostate cancer cell migration and colony formation. Knockout of NHE1 reduced cell migration. The effects of a series of novel NHE1/uPA hexamethylene-amiloride-based inhibitors with varying efficacy towards NHE1 and uPA were examined on prostate cancer cells. Inhibition of NHE1—alone, or with inhibitors combining NHE1 or uPA inhibition—generally did not prevent prostate cancer cell migration. However, uPA inhibition—but not NHE1 inhibition—prevented anchorage-dependent colony formation. Application of inhibitors at concentrations that only saturate uPA inhibition decreased tumor invasion in vivo. The results suggest that while knockout of NHE1 affects cell migration, these effects are not due to NHE1-dependent proton translocation. Additionally, while neither NHE1 nor uPA activity was critical in cell migration, only uPA activity appeared to be critical in anchorage-dependent colony formation of DU 145 prostate cancer cells and invasion in vivo. |
format | Online Article Text |
id | pubmed-8705693 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-87056932021-12-25 Roles of the Na(+)/H(+) Exchanger Isoform 1 and Urokinase in Prostate Cancer Cell Migration and Invasion Li, Xiuju Buckley, Benjamin Stoletov, Konstantin Jing, Yang Ranson, Marie Lewis, John D. Kelso, Mike Fliegel, Larry Int J Mol Sci Article Prostate cancer is a leading cause of cancer-associated deaths in men over 60 years of age. Most patients are killed by tumor metastasis. Recent evidence has implicated a role of the tumor microenvironment and urokinase plasminogen activator (uPA) in cancer cell migration, invasion, and metastasis. Here, we examine the role of the Na(+)/H(+) exchanger isoform 1 (NHE1) and uPA in DU 145 prostate cancer cell migration and colony formation. Knockout of NHE1 reduced cell migration. The effects of a series of novel NHE1/uPA hexamethylene-amiloride-based inhibitors with varying efficacy towards NHE1 and uPA were examined on prostate cancer cells. Inhibition of NHE1—alone, or with inhibitors combining NHE1 or uPA inhibition—generally did not prevent prostate cancer cell migration. However, uPA inhibition—but not NHE1 inhibition—prevented anchorage-dependent colony formation. Application of inhibitors at concentrations that only saturate uPA inhibition decreased tumor invasion in vivo. The results suggest that while knockout of NHE1 affects cell migration, these effects are not due to NHE1-dependent proton translocation. Additionally, while neither NHE1 nor uPA activity was critical in cell migration, only uPA activity appeared to be critical in anchorage-dependent colony formation of DU 145 prostate cancer cells and invasion in vivo. MDPI 2021-12-09 /pmc/articles/PMC8705693/ /pubmed/34948058 http://dx.doi.org/10.3390/ijms222413263 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Li, Xiuju Buckley, Benjamin Stoletov, Konstantin Jing, Yang Ranson, Marie Lewis, John D. Kelso, Mike Fliegel, Larry Roles of the Na(+)/H(+) Exchanger Isoform 1 and Urokinase in Prostate Cancer Cell Migration and Invasion |
title | Roles of the Na(+)/H(+) Exchanger Isoform 1 and Urokinase in Prostate Cancer Cell Migration and Invasion |
title_full | Roles of the Na(+)/H(+) Exchanger Isoform 1 and Urokinase in Prostate Cancer Cell Migration and Invasion |
title_fullStr | Roles of the Na(+)/H(+) Exchanger Isoform 1 and Urokinase in Prostate Cancer Cell Migration and Invasion |
title_full_unstemmed | Roles of the Na(+)/H(+) Exchanger Isoform 1 and Urokinase in Prostate Cancer Cell Migration and Invasion |
title_short | Roles of the Na(+)/H(+) Exchanger Isoform 1 and Urokinase in Prostate Cancer Cell Migration and Invasion |
title_sort | roles of the na(+)/h(+) exchanger isoform 1 and urokinase in prostate cancer cell migration and invasion |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8705693/ https://www.ncbi.nlm.nih.gov/pubmed/34948058 http://dx.doi.org/10.3390/ijms222413263 |
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