Tumor-suppressive activity of Lunatic Fringe in prostate through differential modulation of Notch receptor activation.

摘要: Elevated Notch ligand and receptor expression has been associated with aggressive forms of prostate cancer, suggesting a role for signaling in regulation tumor initiation progression. Here, we report critical Lunatic Fringe (Lfng), which encodes an O-fucosylpeptide 3-s-N-acetylglucosaminyltransferase known to modify epidermal growth factor repeats proteins, epithelial differentiation proliferation, as well suppression. Deletion Lfng mice caused altered activation the prostate, elevated accumulation Notch1, Notch2, Notch4 intracellular domains, decreased levels putative Notch3 fragment, increased Hes1, Hes5, Hey2. Loss resulted expansion basal layer, proliferation both luminal cells, ultimately, prostatic intraepithelial neoplasia. The Lfng-null showed down-regulation suppressor gene NKX3.1 androgen expression. Interestingly, LFNG were positively correlated publically available human cancer data sets. Knockdown DU-145 cells led CD44(+)CD24(-) CD49f(+)CD24(-) stem/progenitor-like cell population enhanced prostatosphere-forming capacity. Taken together, these revealed tumor-suppressive through differential signaling.