Olfactomedin 4 Suppresses Prostate Cancer Cell Growth and Metastasis via Negativ

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Olfactomedin 4 (OLFM4) is expressed in normal prostate epithelial cells and immortalized normal human prostate epithelial cells (RWPE1), but the identity of OLFM4-expressing cells within these populations and OLFM4s physiological functions in these cells have not been elucidated. We found here that OLFM4 was expressed in multiple stem/progenitor-like cell populations, and was frequently co-expressed with KRT13 and LY6D by performing single cell RNA sequencing analysis. Functionally, OLFM4-knockout RWPE1 cells exhibited enhanced proliferation of CD44+/CD49F+ stem/progenitor-like cell population and interrupted CD24+luminal lineage progenitor cell differentiation when compared with OLFM4-wild RWPE1 cells. Molecular and signaling pathway studies revealed an increase in the WNT/APC/MYC signaling pathway gene signature, as well as that of MYC target genes that regulate the cell cycle, in OLFM4-knockout RWPE1 cells. These findings identified that OLFM4 is co-expressing with multiple stem/progenitor cell marker genes and acts as a novel mediator in prostate stem/progenitor cell proliferation and differentiation. Taken together, these findings suggest that OLFM4 plays important role in proliferation and differentiation of prostate stem/progenitor cells through majority mediation of WNT/APC/MYC signaling.