A novel oncogenic axis involving the ETS factor ESE3/EHF, miR-424, COP1 and STAT3 drives prostate tumor progression

Diplôme Thèse A novel oncogenic axis involving the ETS factor ESE3/EHF, miR-424, COP1 and STAT3 drives prostate tumor progression eng 2016-07-04 author Dallavalle Cécilia 809495 director Scapozza Leonardo 600318 director Carbone Giuseppina 10.13097/archive-ouverte/unige:94032 urn:nbn:ch:unige-940326 Sc. 4950 Clinical behavior of prostate cancer (PCa) ranges from indolent disease to very aggressive tumors that rapidly progress to castration-resistance. However, the molecular mechanisms contributing to progression and clinical heterogeneity of PCa are still poorly understood. In this study we defined a novel oncogenic pathway involving miR-424 up-regulation and leading to altered stability of key oncogenic transcription factors, including STAT3. We found that miR-424 targets the E3 ubiquitin ligase COP1 and identified STAT3 as a key substrate of COP1 promoting tumorigenic and cancer stem-like properties in prostate epithelial cells. This oncogenic pathway is preferentially activated in a subgroup of prostate tumors characterized by reduced expression of the ETS factor ESE3/EHF and is associated with disease progression in prostate cancers. Monitoring the state of miR-424/COP1/STAT3 oncogenic axis could provide new insights for the development of specific therapeutic strategies and the identification of patients more likely to have aggressive tumor and disease recurrence. Dewey 615 31 Section des sciences pharmaceutiques 17 false 339164d0-598a-49d0-8e25-b213d2e28057 Thesis Public Thesis Dallavalle Cecilia.pdf 6922351 application/pdf openAccess Faculté des sciences / Section des sciences pharmaceutiques

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A novel oncogenic axis involving the ETS factor ESE3/EHF, miR-424, COP1 and STAT3 drives prostate tumor progression				2016	857	652

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Dallavalle, Cécilia