Signal Crosstalk and the Role of Estrogen Receptor beta (ERβ) in Prostate Cancer

Prostate cancer remains the most prevalent cancer among men worldwide; however, as a sex hormone-dependent cancer, sex hormones and their receptor signaling play an important role in the development and progression of cancer. Most current treatment options for prostate cancer thus revolve around the inhibition of androgen signaling (eg, ADT), which, although effective in the early stages, eventually progresses to treatment-resistant prostate cancer with no effective follow-up options. Recent studies have shown that among the nuclear receptor family members, in addition to androgen receptors, estrogen receptor (ER) plays an important biological function as a transcription factor and regulatory protein in various cancers, acting either directly or indirectly by forming homodimers or heterodimers with ligands. In this paper, we review the application of ERβ in animal models and in vitro experiments in the last 5 years, as well as the presence and role of some of its splice variants. We summarize the overview and update of ERβ in prostate cancer, and provide a corresponding analysis of some current research disagreements. Its crosstalk action on some important cancer growth-related signaling pathways (eg, TGF-β and ERK), regulation of downstream target proteins (eg, nuclear translocation of EGFR and expression of oncogenic-related protein MMP-2), and interactions with related ERβ co-regulators (eg, ZFHX3), agonists, and antagonists in prostate cancer are highlighted, and the resulting effects on tumor progression are described. In addition, the paper describes its current potential clinical application as a novel therapeutic strategy and some of the challenges it faces.