Nevertheless, CRPCa remains fatal due to development of therapy resistance. However, CRPCa remains dependent on AR signaling and therefore the new generation of AR antagonists is, at least initially, beneficial to repress AR signaling also in CRPCa ( 7- 9). Unfortunately, contrary to the primary successful treatment, the advanced PCa growth becomes androgen-independent, so called castration-resistant prostate cancer (CRPCa) ( 6). Therefore, androgen deprivation therapy (ADT) mostly by chemical castration in combination with AR-antagonists is applied for treatment to inactivate the transcriptional transactivation of the AR ( 4). Studies indicate that the androgen-activated AR plays an outstanding role for the development and growth of the normal prostate and also in promoting tumorigenesis of PCa ( 5). However, some tumors advance to invasive form ( 4). The localized primary PCa is treated successfully in initial phases of tumorigenesis by radical prostatectomy and/or radiotherapy. PCa is associated with a high mortality rate ranking among the top causes of cancer deaths in men ( 3). 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.Īn important issue in understanding PCa tumorigenesis is the need for detailed analysis of the progression of PCa from a curable stage to the fatal cancer. Notably, in PCa the phosphorylation of eIF4E is increased ( 2). The phosphorylated form of eIF4E is more active and increases tumorigenicity. Also eIF4E is regulated by phosphorylation. Importantly, the androgen dihydrotestosterone increases the level of 4E-BP1 ( 1). Various kinases were shown to hyper-phosphorylate 4E-BP1, which results in release from eIF4E and subsequent cap-dependent translation ( 2). 4E-BP1 in its hypo-phosphorylated form represses the translational initiation by binding to eIF4E, a key driver of translational initiation and elongation. Authors explored the observation that androgen-activated AR decreases translation in PCa, reduces PCa tumor growth and improves survival in preclinical models ( 1). The link between AR signaling and its interaction with 4E-BP1 expression is an interesting signaling cross-talk in prostate cancer (PCa). 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 androgen receptor regulates a druggable translational regulon in advanced prostate cancer. Email: on: Liu Y, Horn JL, Banda K, et al. Institute of Human Genetics, Jena University Hospital, Am Klinikum 1, 07747 Jena, Germany. Interviews with Outstanding Guest EditorsĬorrespondence to: Aria Baniahmad.Policy of Dealing with Allegations of Research Misconduct.Policy of Screening for Plagiarism Process.
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