FIGURE 8.

A,B, Proposed model of WNT10B action in prostate epithelial cells. Early expression of WNT10B is implicated in determination of undifferentiated UGE and rapid decrease to basal levels is necessary to permit controlled and normal prostate gland growth. In localized PCa, a decrease in WNT10B levels from PIN to PCa results in loss of WNT10B’s antiproliferative function resulting in a hyperproliferative state conducive for tumor formation. As disease advances with dedifferentiation, a stage reminiscent of stem-like undifferentiated epithelium, WNT10B is also reexpressed. In this context of advanced disease, loss of WNT10B results in a reduction of stemness potential, a reversal of EMT, and ultimately an inability to metastatically propagate tumor growth. ECM, extracellular matrix; EMT, epithelial to mesenchymal transition; PCa, prostate cancer; PIN, prostate intraepithelial neoplasia; UGE, urogenital sinus epithelium