Basal Progenitors Contribute to Repair of the Prostate Epithelium Following Induced Luminal Anoikis

Summary Contact with the extracellular matrix is essential for maintenance of epithelial cells in many tissues, while in its absence epithelial cells can detach and undergo anoikis. Here, we show that anoikis of luminal cells in the prostate epithelium is followed by a program of tissue repair that is mediated in part by differentiation of basal epithelial cells to luminal cells. We describe a mouse model in which inducible deletion of E-cadherin in prostate luminal cells results in their apoptotic cell death by anoikis, in the absence of phenotypic effects in the surrounding stroma. Quantitative assessments of proliferation and cell death in the luminal and basal compartments indicate that basal cells can rapidly generate luminal cells. Thus, our findings identify a role for basal-to-luminal differentiation in prostate epithelial repair, and provide a normal context to analogous processes that may occur during prostate cancer initiation.
Graphical Abstract
Highlights • Induced deletion of E-cadherin results in anoikis of prostate luminal cells • Luminal anoikis and tissue repair take place in the absence of stromal phenotypes • Basal cells proliferate and differentiate to produce luminal cells during repair • These findings suggest a conserved role for basal cells in epithelial tissue repair
In this article, Shen and colleagues show that deletion of E-cadherin in prostate luminal epithelial cells results in their death due to anoikis, followed by a process of tissue repair that is mediated in part by basal epithelial progenitors. This latent activity of prostate basal cells demonstrates their context-dependent behavior in response to tissue injury.