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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. and Collins, Anne T. 2019. The putative tumour suppressor protein Latexin is secreted by prostate luminal cells and is downregulated in malignancy. Scientific Reports 9 (1) , 5120. 10.1038/s41598-019-41379-8

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Nature Publishing Group
ISSN: 2045-2322
Date of First Compliant Deposit: 3 April 2019
Date of Acceptance: 28 February 2019
Last Modified: 31 May 2019 20:32
URI: http://orca.cf.ac.uk/id/eprint/121358

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