Pioneer of prostate cancer: past, present and the future ofFOXA1

Prostate cancer is the most commonly diagnosed non-cutaneous cancers in North American men. While androgen deprivation has remained as the cornerstone of prostate cancer treatment, resistance ensues leading to lethal disease.Forkhead box A1(FOXA1) encodes a pioneer factor that induces open chromatin conformation to allow the binding of other transcription factors. Through direct interactions with the Androgen Receptor (AR), FOXA1 helps to shape AR signaling that drives the growth and survival of normal prostate and prostate cancer cells. FOXA1 also possesses an AR-independent role of regulating epithelial-to-mesenchymal transition (EMT). In prostate cancer, mutations converge onto the coding sequence andcis-regulatory elements (CREs) ofFOXA1, leading to functional alterations. In addition, FOXA1 activity in prostate cancer can be modulated post-translationally through various mechanisms such as LSD1-mediated protein demethylation. In this review, we describe the latest discoveries related to the function and regulation of FOXA1 in prostate cancer, pointing to their relevance to guide future clinical interventions.

Automated summary

Prostate cancer, the most commonly diagnosed non-cutaneous cancer in North American men, is often treated with androgen deprivation therapy. However, resistance can develop, leading to lethal disease. FOXA1, a pioneer factor that helps shape and regulate androgen receptor signaling, plays a crucial role in prostate cancer development and progression. Mutations in FOXA1 can result in functional alterations, and post-translational modifications can also modulate its activity in prostate cancer. Identifying the function and regulation of FOXA1 in prostate cancer is important for guiding future clinical interventions.