The putative tumour suppressor protein Latexin is secreted by prostate luminal cells and is downregulated in malignancy

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The putative tumour suppressor protein Latexin is secreted by prostate luminal cells and is downregulated in malignancy. / Seed, RI; Taurozzi, AJ; Wilcock, DJ; Nappo, G; Erb, HHH; Read, ML; Gurney, M; Archer, LK; Ito, S; Rumsby, MG; Petrie, JL; Clayton, A; Maitland, NJ; Collins, AT.

In: Scientific Reports, Vol. 9, 5120, 26.03.2019.

Research output: Contribution to journalArticle

Harvard

Seed, RI, Taurozzi, AJ, Wilcock, DJ, Nappo, G, Erb, HHH, Read, ML, Gurney, M, Archer, LK, Ito, S, Rumsby, MG, Petrie, JL, Clayton, A, Maitland, NJ & Collins, AT 2019, 'The putative tumour suppressor protein Latexin is secreted by prostate luminal cells and is downregulated in malignancy', Scientific Reports, vol. 9, 5120. https://doi.org/10.1038/s41598-019-41379-8

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Seed, RI ; Taurozzi, AJ ; Wilcock, DJ ; Nappo, G ; Erb, HHH ; Read, ML ; Gurney, M ; Archer, LK ; Ito, S ; Rumsby, MG ; Petrie, JL ; Clayton, A ; Maitland, NJ ; Collins, AT. / The putative tumour suppressor protein Latexin is secreted by prostate luminal cells and is downregulated in malignancy. In: Scientific Reports. 2019 ; Vol. 9.

Bibtex

@article{4343c0ee56f745faaee287ec8f395f09,
title = "The putative tumour suppressor protein Latexin is secreted by prostate luminal cells and is downregulated in malignancy",
abstract = "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.",
author = "RI Seed and AJ Taurozzi and DJ Wilcock and G Nappo and HHH Erb and ML Read and M Gurney and LK Archer and S Ito and MG Rumsby and JL Petrie and A Clayton and NJ Maitland and AT Collins",
year = "2019",
month = "3",
day = "26",
doi = "10.1038/s41598-019-41379-8",
language = "English",
volume = "9",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

RIS

TY - JOUR

T1 - The putative tumour suppressor protein Latexin is secreted by prostate luminal cells and is downregulated in malignancy

AU - Seed, RI

AU - Taurozzi, AJ

AU - Wilcock, DJ

AU - Nappo, G

AU - Erb, HHH

AU - Read, ML

AU - Gurney, M

AU - Archer, LK

AU - Ito, S

AU - Rumsby, MG

AU - Petrie, JL

AU - Clayton, A

AU - Maitland, NJ

AU - Collins, AT

PY - 2019/3/26

Y1 - 2019/3/26

N2 - 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.

AB - 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.

UR - http://europepmc.org/abstract/med/30914656

U2 - 10.1038/s41598-019-41379-8

DO - 10.1038/s41598-019-41379-8

M3 - Article

C2 - 30914656

VL - 9

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 5120

ER -