Basal epithelial cells in prostate development, tumorigenesis, and cancer progression

The prostate epithelium is composed of two predominant cell populations: luminal and basal epithelial cells. Luminal cells have a secretory function that supports male fertility while basal cells function in regeneration and maintenance of epithelial tissue. Recent studies in humans and mice have expanded our knowledge of the role and regulation of luminal and basal cells in prostate organogenesis, development, and homeostasis. The insights from healthy prostate biology can inform studies focused on the origins of prostate cancer, progression of the disease, and development of resistance to targeted hormonal therapies. In this review, we discuss a critical role for basal cells in the development and maintenance of healthy prostate tissue. Additionally, we provide evidence supporting a role for basal cells in oncogenesis and therapeutic resistance mechanisms of prostate cancer. Finally, we describe basal cell regulators that may promote lineage plasticity and basal cell identity in prostate cancers that have developed therapeutic resistance. These regulators could serve as therapeutic targets to inhibit or delay resistance and thereby improve outcomes for prostate cancer patients.