Olfactomedin 4 Suppresses Prostate Cancer Cell Growth and Metastasis via Negativ

National Heart, Lung, And Blood Institute

Investigators

Linked publications & trials

Abstract

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. Using single-cell RNA sequencing analysis, we found that OLFM4 was expressed in multiple stem/progenitor-like cell populations in the normal prostate epithelium and RWPE1 cells and was frequently co-expressed with KRT13 and LY6D in RWPE1 cells. Functionally, OLFM4-knockout RWPE1 cells exhibited enhanced proliferation of the CD44+/CD49F+ stem/progenitor-like cell population and interrupted CD24+ luminal lineage progenitor cell differentiation when compared with OLFM4-wild RWPE1 cells. In addition, molecular and signaling pathway studies revealed an increase in the WNT/APC/MYC signaling pathway gene signature and MYC target genes that regulate multiple biological processes in OLFM4-knockout RWPE1 cells. These findings indicated that OLFM4 is co-expressed with multiple stem/progenitor cell marker genes in prostate epithelial cells and is a novel mediator in prostate stem/progenitor cell proliferation and differentiation.