Androgen-regulated transcription of ESRP2 drives alternative splicing patterns in prostate cancer
dc.contributor.author | Munkley, J | |
dc.contributor.author | Ling, L | |
dc.contributor.author | Krishnan, SRG | |
dc.contributor.author | Hysenaj, G | |
dc.contributor.author | Scott, E | |
dc.contributor.author | Dalgliesh, C | |
dc.contributor.author | Oo, HZ | |
dc.contributor.author | Maia, TM | |
dc.contributor.author | Cheung, K | |
dc.contributor.author | Ehrmann, I | |
dc.contributor.author | Livermore, KE | |
dc.contributor.author | Zielinska, H | |
dc.contributor.author | Thompson, O | |
dc.contributor.author | Knight, B | |
dc.contributor.author | McCullagh, P | |
dc.contributor.author | McGrath, J | |
dc.contributor.author | Crundwell, M | |
dc.contributor.author | Harries, LW | |
dc.contributor.author | Daugaard, M | |
dc.contributor.author | Cockell, S | |
dc.contributor.author | Barbosa-Morais, NL | |
dc.contributor.author | Oltean, S | |
dc.contributor.author | Elliott, DJ | |
dc.date.accessioned | 2019-09-10T13:53:31Z | |
dc.date.issued | 2019-09-03 | |
dc.description.abstract | Prostate is the most frequent cancer in men. Prostate cancer progression is driven by androgen steroid hormones, and delayed by androgen deprivation therapy (ADT). Androgens control transcription by stimulating androgen receptor (AR) activity, yet also control pre-mRNA splicing through less clear mechanisms. Here we find androgens regulate splicing through AR-mediated transcriptional control of the epithelial-specific splicing regulator ESRP2. Both ESRP2 and its close paralog ESRP1 are highly expressed in primary prostate cancer. Androgen stimulation induces splicing switches in many endogenous ESRP2-controlled mRNA isoforms, including splicing switches correlating with disease progression. ESRP2 expression in clinical prostate cancer is repressed by ADT, which may thus inadvertently dampen epithelial splice programmes. Supporting this, treatment with the AR antagonist bicalutamide (Casodex®) induced mesenchymal splicing patterns of genes including FLNB and CTNND1. Our data reveals a new mechanism of splicing control in prostate cancer with important implications for disease progression. | en_GB |
dc.description.sponsorship | Prostate Cancer UK | en_GB |
dc.description.sponsorship | Biotechnology and Biological Sciences Research Council (BBSRC) | en_GB |
dc.description.sponsorship | Terry Fox Research Institute | en_GB |
dc.description.sponsorship | Breast Cancer Now | en_GB |
dc.identifier.citation | Vol. 8, article e47678 | en_GB |
dc.identifier.doi | 10.7554/eLife.47678 | |
dc.identifier.grantnumber | PG12-34 | en_GB |
dc.identifier.grantnumber | BB/P006612/1 | en_GB |
dc.identifier.grantnumber | TFRI-NF-PPG | en_GB |
dc.identifier.grantnumber | 2014NovPR355 | en_GB |
dc.identifier.grantnumber | RIA16-ST2-011 | en_GB |
dc.identifier.other | 47678 | |
dc.identifier.uri | http://hdl.handle.net/10871/38654 | |
dc.language.iso | en | en_GB |
dc.publisher | eLife Sciences Publications | en_GB |
dc.relation.url | https://www.ncbi.nlm.nih.gov/pubmed/31478829 | en_GB |
dc.rights | © 2019, Munkley et al. Open access. This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited. | en_GB |
dc.subject | chromosomes | en_GB |
dc.subject | gene expression | en_GB |
dc.subject | human | en_GB |
dc.title | Androgen-regulated transcription of ESRP2 drives alternative splicing patterns in prostate cancer | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2019-09-10T13:53:31Z | |
exeter.place-of-publication | England | en_GB |
dc.description | This is the final version. Available on open access from eLife Sciences Publications via the DOI in this record | en_GB |
dc.description | Data availability: Sequencing data have been deposited in GEO under accession code GSE129540. | en_GB |
dc.identifier.journal | ELife | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2019-09-02 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2019-09-03 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2019-09-10T13:44:39Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2019-09-10T13:53:33Z | |
refterms.panel | A | en_GB |
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This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.