Journal article
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:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 1.9MB, Terms of use)
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- Publisher copy:
- 10.1038/bjc.2016.402
Authors
+ European Union
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- Grant:
- FP7 Marie Curie Initial Training Network PRO-NEST (grant number 238278
- Publisher:
- Cancer Research UK
- Journal:
- British Journal of Cancer More from this journal
- Volume:
- 116
- Issue:
- 2
- Pages:
- 227–236
- Publication date:
- 2016-12-22
- DOI:
- EISSN:
-
1532-1827
- ISSN:
-
0007-0920
- Language:
-
English
- Keywords:
- Pubs id:
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pubs:667158
- UUID:
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uuid:45dcd7d3-5ae0-4393-9153-d2f611566efc
- Local pid:
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pubs:667158
- Deposit date:
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2017-01-10
Terms of use
- Copyright holder:
- Cancer Research UK
- Copyright date:
- 2016
- Notes:
-
Copyright © 2016 Cancer Research UK. This work is licensed under the Creative Commons
Attribution 4.0 International License. To view a copy
of this license, visit http://creativecommons.org/licenses/by/4.0/
- Licence:
- CC Attribution (CC BY)
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