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

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Carbone, Giuseppina
Defense Thèse de doctorat : Univ. Genève, 2016 - Sc. 4950 - 2016/07/04
Abstract 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.
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URN: urn:nbn:ch:unige-940326
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DALLAVALLE, Cécilia. A novel oncogenic axis involving the ETS factor ESE3/EHF, miR-424, COP1 and STAT3 drives prostate tumor progression. Université de Genève. Thèse, 2016. https://archive-ouverte.unige.ch/unige:94032

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Deposited on : 2017-05-08

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