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Buczek, M.E., Miles, A.K. 
ORCID: 0000-0002-5388-938X, Green, W., Johnson, C., Boocock, D.J. ORCID: 0000-0002-7333-3549, Pockley, A.G. ORCID: 0000-0001-9593-6431, Rees, R.C. ORCID: 0000-0002-4574-4746, Hulman, G., Van Schalkwyk, G., Parkinson, R., Hulman, J., Powe, D.G. and Regad, T. ORCID: 0000-0003-4028-6368,
2016.
Cytoplasmic PML promotes TGF-β-associated epithelial–mesenchymal transition and invasion in prostate cancer.
Oncogene, 35, pp. 3465-3475.
ISSN 0950-9232
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Abstract
Epithelial–mesenchymal transition (EMT) is a key event that is involved in the invasion and dissemination of cancer cells. Although typically considered as having tumour-suppressive properties, transforming growth factor (TGF)-β signalling is altered during cancer and has been associated with the invasion of cancer cells and metastasis. In this study, we report a previously unknown role for the cytoplasmic promyelocytic leukaemia (cPML) tumour suppressor in TGF-β signalling-induced regulation of prostate cancer-associated EMT and invasion. We demonstrate that cPML promotes a mesenchymal phenotype and increases the invasiveness of prostate cancer cells. This event is associated with activation of TGF-β canonical signalling pathway through the induction of Sma and Mad related family 2 and 3 (SMAD2 and SMAD3) phosphorylation. Furthermore, the cytoplasmic localization of promyelocytic leukaemia (PML) is mediated by its nuclear export in a chromosomal maintenance 1 (CRM1)-dependent manner. This was clinically tested in prostate cancer tissue and shown that cytoplasmic PML and CRM1 co-expression correlates with reduced disease-specific survival. In summary, we provide evidence of dysfunctional TGF-β signalling occurring at an early stage in prostate cancer. We show that this disease pathway is mediated by cPML and CRM1 and results in a more aggressive cancer cell phenotype. We propose that the targeting of this pathway could be therapeutically exploited for clinical benefit.
| Item Type: | Journal article | ||||||
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| Publication Title: | Oncogene | ||||||
| Creators: | Buczek, M.E., Miles, A.K., Green, W., Johnson, C., Boocock, D.J., Pockley, A.G., Rees, R.C., Hulman, G., Van Schalkwyk, G., Parkinson, R., Hulman, J., Powe, D.G. and Regad, T. | ||||||
| Publisher: | Nature Publishing Group | ||||||
| Date: | 2016 | ||||||
| Volume: | 35 | ||||||
| ISSN: | 0950-9232 | ||||||
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| Rights: | © 2015 Macmillan Publishers Limited. All rights reserved. OPEN. | ||||||
| Divisions: | Schools > School of Science and Technology | ||||||
| Record created by: | Jill Tomkinson | ||||||
| Date Added: | 24 Nov 2015 14:35 | ||||||
| Last Modified: | 11 Oct 2021 13:25 | ||||||
| URI: | https://irep.ntu.ac.uk/id/eprint/26466 |
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