Publication: Dual functions of SPOP and ERG dictate androgen therapy responses in prostate cancer.
cris.virtualsource.author-orcid | 21de48df-8f5d-4bb4-8ca1-8fcaa87778cf | |
cris.virtualsource.author-orcid | 525155e4-af3a-4505-b350-0410e7ccadcb | |
cris.virtualsource.author-orcid | ed4d4372-d248-4a7d-b76c-5a104bd1af2d | |
datacite.rights | open.access | |
dc.contributor.author | Bernasocchi, Tiziano | |
dc.contributor.author | El Tekle, Geniver | |
dc.contributor.author | Bolis, Marco | |
dc.contributor.author | Mutti, Azzurra | |
dc.contributor.author | Vallerga, Arianna | |
dc.contributor.author | Brandt, Laura Patricia | |
dc.contributor.author | Spriano, Filippo | |
dc.contributor.author | Svinkina, Tanya | |
dc.contributor.author | Zoma, Marita | |
dc.contributor.author | Ceserani, Valentina | |
dc.contributor.author | Rinaldi, Anna | |
dc.contributor.author | Janouskova, Hana | |
dc.contributor.author | Bossi, Daniela | |
dc.contributor.author | Cavalli, Manuela | |
dc.contributor.author | Mosole, Simone | |
dc.contributor.author | Geiger, Roger | |
dc.contributor.author | Dong, Ze | |
dc.contributor.author | Yang, Cai-Guang | |
dc.contributor.author | Albino, Domenico | |
dc.contributor.author | Rinaldi, Andrea | |
dc.contributor.author | Schraml, Peter | |
dc.contributor.author | Linder, Simon | |
dc.contributor.author | Carbone, Giuseppina M | |
dc.contributor.author | Alimonti, Andrea | |
dc.contributor.author | Bertoni, Francesco | |
dc.contributor.author | Moch, Holger | |
dc.contributor.author | Carr, Steven A | |
dc.contributor.author | Zwart, Wilbert | |
dc.contributor.author | Kruithof-de Julio, Marianna | |
dc.contributor.author | Rubin, Mark Andrew | |
dc.contributor.author | Udeshi, Namrata D | |
dc.contributor.author | Theurillat, Jean-Philippe P | |
dc.date.accessioned | 2024-09-21T16:15:44Z | |
dc.date.available | 2024-09-21T16:15:44Z | |
dc.date.issued | 2021-02-02 | |
dc.description.abstract | Driver genes with a mutually exclusive mutation pattern across tumor genomes are thought to have overlapping roles in tumorigenesis. In contrast, we show here that mutually exclusive prostate cancer driver alterations involving the ERG transcription factor and the ubiquitin ligase adaptor SPOP are synthetic sick. At the molecular level, the incompatible cancer pathways are driven by opposing functions in SPOP. ERG upregulates wild type SPOP to dampen androgen receptor (AR) signaling and sustain ERG activity through degradation of the bromodomain histone reader ZMYND11. Conversely, SPOP-mutant tumors stabilize ZMYND11 to repress ERG-function and enable oncogenic androgen receptor signaling. This dichotomy regulates the response to therapeutic interventions in the AR pathway. While mutant SPOP renders tumor cells susceptible to androgen deprivation therapies, ERG promotes sensitivity to high-dose androgen therapy and pharmacological inhibition of wild type SPOP. More generally, these results define a distinct class of antagonistic cancer drivers and a blueprint toward their therapeutic exploitation. | |
dc.description.sponsorship | Department for BioMedical Research (DBMR) | |
dc.description.sponsorship | Department for BioMedical Research, Forschungsgruppe Präzisionsonkologie | |
dc.description.sponsorship | Universitätsklinik für Urologie | |
dc.identifier.doi | 10.48350/159672 | |
dc.identifier.pmid | 33531470 | |
dc.identifier.publisherDOI | 10.1038/s41467-020-20820-x | |
dc.identifier.uri | https://boris-portal.unibe.ch/handle/20.500.12422/45809 | |
dc.language.iso | en | |
dc.publisher | Nature Publishing Group | |
dc.relation.ispartof | Nature communications | |
dc.relation.issn | 2041-1723 | |
dc.relation.organization | 4E745CF42DBF6EC0E053960C5C82F4E9 | |
dc.relation.organization | DCD5A442BD18E17DE0405C82790C4DE2 | |
dc.relation.organization | DCD5A442BE73E17DE0405C82790C4DE2 | |
dc.relation.organization | DCD5A442C238E17DE0405C82790C4DE2 | |
dc.subject.ddc | 600 - Technology::610 - Medicine & health | |
dc.title | Dual functions of SPOP and ERG dictate androgen therapy responses in prostate cancer. | |
dc.type | article | |
dspace.entity.type | Publication | |
oaire.citation.issue | 1 | |
oaire.citation.startPage | 734 | |
oaire.citation.volume | 12 | |
oairecerif.author.affiliation | Department for BioMedical Research (DBMR) | |
oairecerif.author.affiliation | Universitätsklinik für Urologie | |
oairecerif.author.affiliation | Department for BioMedical Research, Forschungsgruppe Präzisionsonkologie | |
oairecerif.author.affiliation2 | Department for BioMedical Research, Forschungsgruppe Urologie | |
unibe.contributor.role | creator | |
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unibe.date.licenseChanged | 2021-10-13 09:27:55 | |
unibe.description.ispublished | pub | |
unibe.eprints.legacyId | 159672 | |
unibe.journal.abbrevTitle | NAT COMMUN | |
unibe.refereed | true | |
unibe.subtype.article | journal |
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