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Reactivation of the embryonic developmental pathway, epithelial-to-mesenchymal transition (EMT) is associated with prostate cancer (PCa) metastasis and therapy resistance. Recent evidence has demonstrated EMT is stimulated following androgen targeted therapy (ATT). In the present study we investigated the role of EMT transcription factor ZEB1 in ATT-driven EMT, PCa metastasis and drug resistance.

Immunohistochemistry (IHC) staining of ZEB1 on tissue microarrays of primary tumors from clinical samples demonstrated ZEB1 expression correlated with increased tumor aggressiveness and Gleason score. Upon stratification of patient data (n=198), high ZEB1 protein expression correlated with a shorter time to biochemical recurrence (BCR). Furthermore, IHC staining of primary tumours from 148 treatment-naïve patients with and without metastasis demonstrated high ZEB1 levels and correlated to a reduced …