Regulation of mRNA Translation by Hormone Receptors in Breast and Prostate Cancer

Simple Summary The estrogen and androgen receptors (ER, AR) are key oncogenic drivers and therapeutic targets in breast and prostate cancer, respectively. These receptors bind to DNA and regulate gene expression but emerging evidence indicates that they also play important roles in controlling the process of mRNA translation, which dictates cellular protein production. Here, we review the mechanisms by which abnormal activities of ER and AR can dysregulate mRNA translation in breast and prostate cancer cells. Specifically, we explore how the intricate cellular signalling pathways that keep mRNA translation in check are perturbed by aberrant ER and AR signalling, which can lead to enhanced cancer cell growth. We also discuss the potential of targeting mRNA translation as a strategy to treat patients with breast and prostate cancer. Breast and prostate cancer are the second and third leading causes of death amongst all cancer types, respectively. Pathogenesis of these malignancies is characterised by dysregulation of sex hormone signalling pathways, mediated by the estrogen receptor-alpha (ER) in breast cancer and androgen receptor (AR) in prostate cancer. ER and AR are transcription factors whose aberrant function drives oncogenic transcriptional programs to promote cancer growth and progression. While ER/AR are known to stimulate cell growth and survival by modulating gene transcription, emerging findings indicate that their effects in neoplasia are also mediated by dysregulation of protein synthesis (i.e., mRNA translation). This suggests that ER/AR can coordinately perturb both transcriptional and translational programs, resulting in the establishment of proteomes that promote malignancy. In this review, we will discuss relatively understudied aspects of ER and AR activity in regulating protein synthesis as well as the potential of targeting mRNA translation in breast and prostate cancer.

Automated summary

Estrogen and androgen receptors are key drivers in breast and prostate cancer, regulating mRNA translation to influence cellular protein production and enhance cancer cell growth. Targeting mRNA translation could be a potential strategy for treating breast and prostate cancer.