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Oncogenic Role of Secreted Engrailed Homeobox 2 (EN2) in Prostate Cancer
Engrailed variant-2 (EN2) has been suggested as a potential diagnostic biomarker; however, its presence and functional role in prostate cancer (PCa) cells is still controversial or unknown. Here, we analyzed 1) the expression/secretion profile of EN2 in five independent samples cohorts from PCa pati...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780828/ https://www.ncbi.nlm.nih.gov/pubmed/31500112 http://dx.doi.org/10.3390/jcm8091400 |
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author | Gómez-Gómez, Enrique Jiménez-Vacas, Juan M. Pedraza-Arévalo, Sergio López-López, Fernando Herrero-Aguayo, Vicente Hormaechea-Agulla, Daniel Valero-Rosa, José Ibáñez-Costa, Alejandro León-González, Antonio J. Sánchez-Sánchez, Rafael González-Serrano, Teresa Requena-Tapia, Maria J. Castaño, Justo P. Carrasco-Valiente, Julia Gahete, Manuel D. Luque, Raúl M. |
author_facet | Gómez-Gómez, Enrique Jiménez-Vacas, Juan M. Pedraza-Arévalo, Sergio López-López, Fernando Herrero-Aguayo, Vicente Hormaechea-Agulla, Daniel Valero-Rosa, José Ibáñez-Costa, Alejandro León-González, Antonio J. Sánchez-Sánchez, Rafael González-Serrano, Teresa Requena-Tapia, Maria J. Castaño, Justo P. Carrasco-Valiente, Julia Gahete, Manuel D. Luque, Raúl M. |
author_sort | Gómez-Gómez, Enrique |
collection | PubMed |
description | Engrailed variant-2 (EN2) has been suggested as a potential diagnostic biomarker; however, its presence and functional role in prostate cancer (PCa) cells is still controversial or unknown. Here, we analyzed 1) the expression/secretion profile of EN2 in five independent samples cohorts from PCa patients and controls (prostate tissues and/or urine) to determine its utility as a PCa biomarker; and 2) the functional role of EN2 in normal (RWPE1) and tumor (LNCaP/22Rv1/PC3) prostate cells to explore its potential value as therapeutic target. EN2 was overexpressed in our two cohorts of PCa tissues compared to control and in tumor cell lines compared with normal-like prostate cells. This profile was corroborated in silico in three independent data sets [The Cancer Genome Atlas(TCGA)/Memorial Sloan Kettering Cancer Center (MSKCC)/Grasso]. Consistently, urine EN2 levels were elevated and enabled discrimination between PCa and control patients. EN2 treatment increased cell proliferation in LNCaP/22Rv1/PC3 cells, migration in RWPE1/PC3 cells, and PSA secretion in LNCaP cells. These effects were associated, at least in the androgen-sensitive LNCaP cells, with increased AKT and androgen-receptor phosphorylation levels and with modulation of key cancer-associated genes. Consistently, EN2 treatment also regulated androgen-receptor activity (full-length and splicing variants) in androgen-sensitive 22Rv1 cells. Altogether, this study demonstrates the potential utility of EN2 as a non-invasive diagnostic biomarker for PCa and provides novel and valuable information to further investigate its putative utility to develop new therapeutic tools in PCa. |
format | Online Article Text |
id | pubmed-6780828 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-67808282019-10-30 Oncogenic Role of Secreted Engrailed Homeobox 2 (EN2) in Prostate Cancer Gómez-Gómez, Enrique Jiménez-Vacas, Juan M. Pedraza-Arévalo, Sergio López-López, Fernando Herrero-Aguayo, Vicente Hormaechea-Agulla, Daniel Valero-Rosa, José Ibáñez-Costa, Alejandro León-González, Antonio J. Sánchez-Sánchez, Rafael González-Serrano, Teresa Requena-Tapia, Maria J. Castaño, Justo P. Carrasco-Valiente, Julia Gahete, Manuel D. Luque, Raúl M. J Clin Med Article Engrailed variant-2 (EN2) has been suggested as a potential diagnostic biomarker; however, its presence and functional role in prostate cancer (PCa) cells is still controversial or unknown. Here, we analyzed 1) the expression/secretion profile of EN2 in five independent samples cohorts from PCa patients and controls (prostate tissues and/or urine) to determine its utility as a PCa biomarker; and 2) the functional role of EN2 in normal (RWPE1) and tumor (LNCaP/22Rv1/PC3) prostate cells to explore its potential value as therapeutic target. EN2 was overexpressed in our two cohorts of PCa tissues compared to control and in tumor cell lines compared with normal-like prostate cells. This profile was corroborated in silico in three independent data sets [The Cancer Genome Atlas(TCGA)/Memorial Sloan Kettering Cancer Center (MSKCC)/Grasso]. Consistently, urine EN2 levels were elevated and enabled discrimination between PCa and control patients. EN2 treatment increased cell proliferation in LNCaP/22Rv1/PC3 cells, migration in RWPE1/PC3 cells, and PSA secretion in LNCaP cells. These effects were associated, at least in the androgen-sensitive LNCaP cells, with increased AKT and androgen-receptor phosphorylation levels and with modulation of key cancer-associated genes. Consistently, EN2 treatment also regulated androgen-receptor activity (full-length and splicing variants) in androgen-sensitive 22Rv1 cells. Altogether, this study demonstrates the potential utility of EN2 as a non-invasive diagnostic biomarker for PCa and provides novel and valuable information to further investigate its putative utility to develop new therapeutic tools in PCa. MDPI 2019-09-06 /pmc/articles/PMC6780828/ /pubmed/31500112 http://dx.doi.org/10.3390/jcm8091400 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Gómez-Gómez, Enrique Jiménez-Vacas, Juan M. Pedraza-Arévalo, Sergio López-López, Fernando Herrero-Aguayo, Vicente Hormaechea-Agulla, Daniel Valero-Rosa, José Ibáñez-Costa, Alejandro León-González, Antonio J. Sánchez-Sánchez, Rafael González-Serrano, Teresa Requena-Tapia, Maria J. Castaño, Justo P. Carrasco-Valiente, Julia Gahete, Manuel D. Luque, Raúl M. Oncogenic Role of Secreted Engrailed Homeobox 2 (EN2) in Prostate Cancer |
title | Oncogenic Role of Secreted Engrailed Homeobox 2 (EN2) in Prostate Cancer |
title_full | Oncogenic Role of Secreted Engrailed Homeobox 2 (EN2) in Prostate Cancer |
title_fullStr | Oncogenic Role of Secreted Engrailed Homeobox 2 (EN2) in Prostate Cancer |
title_full_unstemmed | Oncogenic Role of Secreted Engrailed Homeobox 2 (EN2) in Prostate Cancer |
title_short | Oncogenic Role of Secreted Engrailed Homeobox 2 (EN2) in Prostate Cancer |
title_sort | oncogenic role of secreted engrailed homeobox 2 (en2) in prostate cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780828/ https://www.ncbi.nlm.nih.gov/pubmed/31500112 http://dx.doi.org/10.3390/jcm8091400 |
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