STAT3/ERP57/TPX2 axis and process of “androgen escape” in prostate cancer

The mechanisms of Prostate Cancer (PCa) progression through hormone-dependent to hormone refractory form is still unclear. Many data indicate that JAK/STAT signaling contributes to tumor resistance and STAT3 hyperactivation is observed in a variety of human cancers. Moreover, several authors suggested that ERp57 (GRP58/PDIA3), a disulfide isomerases protein, is associated with modulation of STAT3 activity. We investigate the role of STAT3-ERp57-TPX2 axis in the ormone-responsive and androgen-refractory tumor using human PCa cell lines, LNCaP (androgen-sensitive) and PC3 (androgen-refractory), untreated and stimulated with IL-6 and EGF. Immunoblotting and CoIP analysis were performed to confirm STAT3 activation and ERp57-STAT3 interaction. To investigate the physiological relevance of STAT3-ERp57-TPX2 axis, we inhibited STAT3 or ERp57 activity and the expression levels of TPX2 was monitored by qRT-PCR. The results showed that increased STAT3-ERp57 complex association determines an TPX2 overexpression. In conclusion, this study showed that STAT3-ERp57-TPX2 axis is correlated with tumor progression and it suggests a functional role of STAT3/ERp57 complex in the Androgen Escape.