Treatment of prostate cancer presents a major challenge as they frequently become resistant to hormone-withdrawal therapy, for which no effective treatment is available. We recently identified a prediction marker of tumor recurrence in GATA3, whereby high GATA3 expression is associated with a better prognosis. In accordance with this, hormone-resistant tumors exclude GATA3 from the nucleus. Our work is aim at understanding how GATA3 is excluded from the nucleus in these tumors, therefore blocking its tumor suppressor function. This will help us understand the important role played by GATA3 during cancer progression, notably concerning its negative regulation by oncogenic pathways and its role in normal and cancer stem cell homeostasis. Finally, this work has immediate relevance to prostate cancer biology and treatment. The fact that GATA3 is still present but mis-localized in hormone-resistant tumors, suggests a therapeutic strategy whereby GATA3 is sent back to the nucleus to restore its tumor suppressor function. This research proposal will therefore advance the mechanistic and biological knowledge necessary for the development of such strategy.