Publication:
Dual functions of SPOP and ERG dictate androgen therapy responses in prostate cancer.

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dc.contributor.authorBernasocchi, Tiziano
dc.contributor.authorEl Tekle, Geniver
dc.contributor.authorBolis, Marco
dc.contributor.authorMutti, Azzurra
dc.contributor.authorVallerga, Arianna
dc.contributor.authorBrandt, Laura Patricia
dc.contributor.authorSpriano, Filippo
dc.contributor.authorSvinkina, Tanya
dc.contributor.authorZoma, Marita
dc.contributor.authorCeserani, Valentina
dc.contributor.authorRinaldi, Anna
dc.contributor.authorJanouskova, Hana
dc.contributor.authorBossi, Daniela
dc.contributor.authorCavalli, Manuela
dc.contributor.authorMosole, Simone
dc.contributor.authorGeiger, Roger
dc.contributor.authorDong, Ze
dc.contributor.authorYang, Cai-Guang
dc.contributor.authorAlbino, Domenico
dc.contributor.authorRinaldi, Andrea
dc.contributor.authorSchraml, Peter
dc.contributor.authorLinder, Simon
dc.contributor.authorCarbone, Giuseppina M
dc.contributor.authorAlimonti, Andrea
dc.contributor.authorBertoni, Francesco
dc.contributor.authorMoch, Holger
dc.contributor.authorCarr, Steven A
dc.contributor.authorZwart, Wilbert
dc.contributor.authorKruithof-de Julio, Marianna
dc.contributor.authorRubin, Mark Andrew
dc.contributor.authorUdeshi, Namrata D
dc.contributor.authorTheurillat, Jean-Philippe P
dc.date.accessioned2024-09-21T16:15:44Z
dc.date.available2024-09-21T16:15:44Z
dc.date.issued2021-02-02
dc.description.abstractDriver 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.sponsorshipDepartment for BioMedical Research (DBMR)
dc.description.sponsorshipDepartment for BioMedical Research, Forschungsgruppe Präzisionsonkologie
dc.description.sponsorshipUniversitätsklinik für Urologie
dc.identifier.doi10.48350/159672
dc.identifier.pmid33531470
dc.identifier.publisherDOI10.1038/s41467-020-20820-x
dc.identifier.urihttps://boris-portal.unibe.ch/handle/20.500.12422/45809
dc.language.isoen
dc.publisherNature Publishing Group
dc.relation.ispartofNature communications
dc.relation.issn2041-1723
dc.relation.organization4E745CF42DBF6EC0E053960C5C82F4E9
dc.relation.organizationDCD5A442BD18E17DE0405C82790C4DE2
dc.relation.organizationDCD5A442BE73E17DE0405C82790C4DE2
dc.relation.organizationDCD5A442C238E17DE0405C82790C4DE2
dc.subject.ddc600 - Technology::610 - Medicine & health
dc.titleDual functions of SPOP and ERG dictate androgen therapy responses in prostate cancer.
dc.typearticle
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oaire.citation.issue1
oaire.citation.startPage734
oaire.citation.volume12
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oairecerif.author.affiliationDepartment for BioMedical Research (DBMR)
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oairecerif.author.affiliationDepartment for BioMedical Research, Forschungsgruppe Präzisionsonkologie
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unibe.date.licenseChanged2021-10-13 09:27:55
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