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The putative tumour suppressor protein Latexin is secreted by prostate luminal cells and is downregulated in malignancy
Loss of latexin (LXN) expression negatively correlates with the prognosis of several human cancers. Despite association with numerous processes including haematopoietic stem cell (HSC) fate, inflammation and tumour suppression, a clearly defined biological role for LXN is still lacking. Therefore, w...
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/PMC6435711/ https://www.ncbi.nlm.nih.gov/pubmed/30914656 http://dx.doi.org/10.1038/s41598-019-41379-8 |
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author | Seed, Robert I. Taurozzi, Alberto J. Wilcock, Daniel J. Nappo, Giovanna Erb, Holger H. H. Read, Martin L. Gurney, Mark Archer, Leanne K. Ito, Saburo Rumsby, Martin G. Petrie, John L. Clayton, Aled Maitland, Norman J. Collins, Anne T. |
author_facet | Seed, Robert I. Taurozzi, Alberto J. Wilcock, Daniel J. Nappo, Giovanna Erb, Holger H. H. Read, Martin L. Gurney, Mark Archer, Leanne K. Ito, Saburo Rumsby, Martin G. Petrie, John L. Clayton, Aled Maitland, Norman J. Collins, Anne T. |
author_sort | Seed, Robert I. |
collection | PubMed |
description | Loss of latexin (LXN) expression negatively correlates with the prognosis of several human cancers. Despite association with numerous processes including haematopoietic stem cell (HSC) fate, inflammation and tumour suppression, a clearly defined biological role for LXN is still lacking. Therefore, we sought to understand LXN expression and function in the normal and malignant prostate to assess its potential as a therapeutic target. Our data demonstrate that LXN is highly expressed in normal prostate luminal cells but downregulated in high Gleason grade cancers. LXN protein is both cytosolic and secreted by prostate cells and expression is directly and potently upregulated by all-trans retinoic acid (atRA). Whilst overexpression of LXN in prostate epithelial basal cells did not affect cell fate, LXN overexpression in the luminal cancer line LNCaP reduced plating efficiency. Transcriptome analysis revealed that LXN overexpression had no direct effects on gene expression but had significant indirect effects on important genes involved in both retinoid metabolism and IFN-associated inflammatory responses. These data highlight a potential role for LXN in retinoid signaling and inflammatory pathways. Investigating the effects of LXN on immune cell function in the tumour microenvironment (TME) may reveal how observed intratumoural loss of LXN affects the prognosis of many adenocarcinomas. |
format | Online Article Text |
id | pubmed-6435711 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-64357112019-04-03 The putative tumour suppressor protein Latexin is secreted by prostate luminal cells and is downregulated in malignancy Seed, Robert I. Taurozzi, Alberto J. Wilcock, Daniel J. Nappo, Giovanna Erb, Holger H. H. Read, Martin L. Gurney, Mark Archer, Leanne K. Ito, Saburo Rumsby, Martin G. Petrie, John L. Clayton, Aled Maitland, Norman J. Collins, Anne T. Sci Rep Article Loss of latexin (LXN) expression negatively correlates with the prognosis of several human cancers. Despite association with numerous processes including haematopoietic stem cell (HSC) fate, inflammation and tumour suppression, a clearly defined biological role for LXN is still lacking. Therefore, we sought to understand LXN expression and function in the normal and malignant prostate to assess its potential as a therapeutic target. Our data demonstrate that LXN is highly expressed in normal prostate luminal cells but downregulated in high Gleason grade cancers. LXN protein is both cytosolic and secreted by prostate cells and expression is directly and potently upregulated by all-trans retinoic acid (atRA). Whilst overexpression of LXN in prostate epithelial basal cells did not affect cell fate, LXN overexpression in the luminal cancer line LNCaP reduced plating efficiency. Transcriptome analysis revealed that LXN overexpression had no direct effects on gene expression but had significant indirect effects on important genes involved in both retinoid metabolism and IFN-associated inflammatory responses. These data highlight a potential role for LXN in retinoid signaling and inflammatory pathways. Investigating the effects of LXN on immune cell function in the tumour microenvironment (TME) may reveal how observed intratumoural loss of LXN affects the prognosis of many adenocarcinomas. Nature Publishing Group UK 2019-03-26 /pmc/articles/PMC6435711/ /pubmed/30914656 http://dx.doi.org/10.1038/s41598-019-41379-8 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 Seed, Robert I. Taurozzi, Alberto J. Wilcock, Daniel J. Nappo, Giovanna Erb, Holger H. H. Read, Martin L. Gurney, Mark Archer, Leanne K. Ito, Saburo Rumsby, Martin G. Petrie, John L. Clayton, Aled Maitland, Norman J. Collins, Anne T. The putative tumour suppressor protein Latexin is secreted by prostate luminal cells and is downregulated in malignancy |
title | The putative tumour suppressor protein Latexin is secreted by prostate luminal cells and is downregulated in malignancy |
title_full | The putative tumour suppressor protein Latexin is secreted by prostate luminal cells and is downregulated in malignancy |
title_fullStr | The putative tumour suppressor protein Latexin is secreted by prostate luminal cells and is downregulated in malignancy |
title_full_unstemmed | The putative tumour suppressor protein Latexin is secreted by prostate luminal cells and is downregulated in malignancy |
title_short | The putative tumour suppressor protein Latexin is secreted by prostate luminal cells and is downregulated in malignancy |
title_sort | putative tumour suppressor protein latexin is secreted by prostate luminal cells and is downregulated in malignancy |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6435711/ https://www.ncbi.nlm.nih.gov/pubmed/30914656 http://dx.doi.org/10.1038/s41598-019-41379-8 |
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