Protein translation controlled by the androgen receptor in prostate cancer: a novel therapeutic option?

Liu et al. identified recently a novel role of the androgen receptor (AR) as a repressor of mRNA-specific translation through increased expression of 4E-BP1 (eukaryotic translation initiation factor 4E (eIF4E)-binding protein), a key factor in eukaryotic translation (1). The link between AR signaling and its interaction with 4E-BP1 expression is an interesting signaling cross-talk in prostate cancer (PCa). Authors explored the observation that androgen-activated AR decreases translation in PCa, reduces PCa tumor growth and improves survival in preclinical models (1). 4E-BP1 in its hypo-phosphorylated form represses the translational initiation by binding to eIF4E, a key driver of translational initiation and elongation. Various kinases were shown to hyper-phosphorylate 4E-BP1, which results in release from eIF4E and subsequent cap-dependent translation (2). Importantly, the androgen dihydrotestosterone increases the level of 4E-BP1 (1). Also eIF4E is regulated by phosphorylation. The phosphorylated form of eIF4E is more active and increases tumorigenicity. Notably, in PCa the phosphorylation of eIF4E is increased (2). The protein levels of each, 4E-BP1 and eIF4E, their interaction, as well as the cross-talk with the androgen-activated AR paves a novel AR signalling pathway in translational control