Endocrine Abstracts

The emergence of prostate cancer and the progression of the disease are significantly driven by the androgen receptor (AR) in combination with other transcription factors. The evolution of aggressive disease requires tumours to become resistant to metabolic stress and subsequently therapeutic stress. Given the role of the prostate gland has a secretory organ characterised by high rates of protein synthesis particularly in AR-positive luminal epithelial cells there are inherent...

MiR-346 is an Androgen Receptor (AR)-activating miR that associates with DNA damage response (DDR)-linked transcripts in prostate cancer (PC). MiR-346 induces rapid and extensive DNA damage in PC cells through chromatin association, activation of transcription, R-loop formation and DNA replication stress, leading to checkpoint activation and cell cycle arrest. MiR-346 interacts with lncRNA, NORAD, in PC cells, which functions to maintain mitosis, DDR, and chromosomal integrity...

Epigenetic reprogramming including altered transcription factor binding and altered patterns of chromatin and DNA modifications are now accepted as the hallmark of aggressive cancers. We show that global changes in chromatin structure and chromatin accessibility in prostate tumour tissue can define castrate-resistant prostate cancer and be used to inform the discovery of gene-level classifiers for therapy. In addition, we show that the androgen receptor overexpression alone, w...

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...