Olfactomedin 4 Suppresses Prostate Cancer Cell Growth and Metastasis via Negativ

Olfactomedin 4 （OLFM4）在正常前列腺上皮细胞和永生化正常人前列腺上皮细胞（RWPE1）中表达，但在这些群体中表达OLFM4的细胞的身份以及OLFM4在这些细胞中的生理功能尚不清楚。通过单细胞RNA测序分析，我们发现OLFM4在多个干细胞/祖细胞样细胞群中表达，并且经常与KRT13和LY6D共表达。功能上，与olfm4 -野生RWPE1细胞相比，olfm4敲除RWPE1细胞表现出CD44+/CD49F+干细胞/祖细胞样细胞群的增殖增强，CD24+管腔谱系祖细胞分化中断。分子和信号通路研究显示，在olfm4敲除RWPE1细胞中，WNT/APC/MYC信号通路基因特征以及MYC调控细胞周期的靶基因特征增加。这些发现表明OLFM4与多个干细胞/祖细胞标记基因共表达，并作为前列腺干细胞/祖细胞增殖和分化的新介质。综上所述，这些发现表明OLFM4通过WNT/APC/MYC信号的大部分介导在前列腺干/祖细胞的增殖和分化中发挥重要作用。

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.