Endocrine Abstracts

Although new treatments for castrate-resistant prostate cancer (CRPC), such as enzalutamide and abiraterone, have shown promise, moderate response rates and development of resistance to these agents has limited their clinical effectiveness. It is therefore vital we improve our understanding of androgen receptor (AR) re-activation in advanced disease, focusing particularly on regulatory processes governing activity of AR mutants and splice variants (AR-Vs), to enable the develo...

Phosphorylation of the Androgen Receptor (AR), has been shown to play an important role in directly modulating AR activity. However, the full extent of which protein kinases are involved in the regulation of the AR remains unknown. In order to address which kinases are important in the regulation of AR activity in both androgen sensitive and independent prostate cancer (PCa), a comprehensive siRNA kinome screen was performed. AR transcriptional regulation was evaluated using a...

We previously demonstrated that USP12 functions as an AR co-activator by directly deubiquitinating the AR and stabilising its protein levels. Additionally, we showed that USP12 targets the PHLPP AKT phosphatases leading to decreased levels of activated, phosphorylated AKT (pAKT) and as such indirectly stabilises the AR preventing its phosphorylation at serine 213. We further investigated the role of USP12 in prostate cancer by analysing the transcriptome of the LNCaP prostate ...

Changes in glycan composition are common in cancer and can play important roles in all of the recognised hallmarks of cancer (1). We recently identified glycosylation as a global target for androgen control in prostate cancer cells and further defined a set of 8 glycosylation enzymes (GALNT7, ST6GalNAc1, GCNT1, UAP1, PGM3, CSGALNACT1, ST6GAL1 and EDEM3), which are also significantly up-regulated in prostate cancer tissue (4). These 8 enzymes are under direct control of the and...