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Reference: Rao, SR, Snaith, AE, Marino, D et al., (2016). Tumour-derived alkaline phosphatase regulates tumour growth, epithelial plasticity and disease-free survival in metastatic prostate cancer. British Journal of Cancer, 116 (2), 227–236.Citable link to this page:

 

Tumour-derived alkaline phosphatase regulates tumour growth, epithelial plasticity and disease-free survival in metastatic prostate cancer

Abstract: BACKGROUND: Recent evidence suggests that bone-related parameters are the main prognostic factors for overall survival in advanced prostate cancer (PCa), with elevated circulating levels of alkaline phosphatase (ALP) thought to reflect the dysregulated bone formation accompanying distant metastases. We have identified that PCa cells express ALPL, the gene that encodes for tissue nonspecific ALP, and hypothesised that tumour-derived ALPL may contribute to disease progression. METHODS: Functional effects of ALPL inhibition were investigated in metastatic PCa cell lines. ALPL gene expression was analysed from published PCa data sets, and correlated with disease-free survival and metastasis. RESULTS: ALPL expression was increased in PCa cells from metastatic sites. A reduction in tumour-derived ALPL expression or ALP activity increased cell death, mesenchymal-to-epithelial transition and reduced migration. Alkaline phosphatase activity was decreased by the EMT repressor Snail. In men with PCa, tumour-derived ALPL correlated with EMT markers, and high ALPL expression was associated with a significant reduction in disease-free survival. CONCLUSIONS: Our studies reveal the function of tumour-derived ALPL in regulating cell death and epithelial plasticity, and demonstrate a strong association between ALPL expression in PCa cells and metastasis or disease-free survival, thus identifying tumour-derived ALPL as a major contributor to the pathogenesis of PCa progression.British Journal of Cancer advance online publication, 22 December 2016; doi:10.1038/bjc.2016.402 www.bjcancer.com.

Publication status:PublishedPeer Review status:Peer reviewedVersion:Publisher's version Funder: European Union   Funder: Cancer Research UK   Notes:Copyright © 2016 Cancer Research UK. This work is licensed under the Creative CommonsAttribution 4.0 International License. To view a copyof this license, visit http://creativecommons.org/licenses/by/4.0/

Bibliographic Details

Publisher: Cancer Research UK

Publisher Website: http://www.cancerresearchuk.org/

Journal: British Journal of Cancersee more from them

Publication Website: http://www.nature.com/bjc/

Volume: 116

Issue: 2

Extent: 227–236

Issue Date: 22 December 2016

pages:227–236Identifiers

Doi: https://doi.org/10.1038/bjc.2016.402

Eissn: 1532-1827

Issn: 0007-0920

Uuid: uuid:45dcd7d3-5ae0-4393-9153-d2f611566efc

Urn: uri:45dcd7d3-5ae0-4393-9153-d2f611566efc

Pubs-id: pubs:667158 Item Description

Type: journal-article;

Language: eng

Version: Publisher's versionKeywords: prostate cancer metastasis alkaline phosphatase bone EMT MET

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Autor: Rao, SR - - - Snaith, AE - - - Marino, D - - - Cheng, X - - - Lwin, ST - - - Orriss, IR - - - Hamdy, FC - - - Edwards, C - Oxford

Fuente: https://ora.ox.ac.uk/objects/uuid:45dcd7d3-5ae0-4393-9153-d2f611566efc



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