Olfactomedin 4 Suppresses Prostate Cancer Cell Growth and Metastasis via Negativ

Olfactomedin 4 通过 Negativ 抑制前列腺癌细胞的生长和转移

基本信息

批准号：
10253822
负责人：
GRIFFIN RODGERS
金额：
$ 40.45万
依托单位：
NATIONAL HEART, LUNG, AND BLOOD INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10253822
关键词：
13q12 14q American Biological Biological Process CD44 gene CXCL12 gene Cadherins Cancer Cell Growth Cancer Etiology Cathepsins Cell Adhesion Cell Cycle Cell Differentiation process Cell Proliferation Cell surface Cells Cessation of life Chromosomes Colon Carcinoma Colonic Neoplasms Diagnosis Ectopic Expression Epithelial Cells Evaluation Exhibits Exons FOXO1A gene Family Family member Genes Goals Human Human Genome In Vitro Inflammation Interruption Knock-out Lectin Loss of Heterozygosity Malignant neoplasm of prostate Mediation Mediator of activation protein Messenger RNA Metastatic Neoplasm to the Bone Molecular Mus Natural Immunity Negativism Neoplasm Metastasis OLFM4 gene Physiological Play Population Prostate Prostatic Neoplasms Proteins Reporting Retinoblastoma Role Seminal fluid Serum Signal Pathway Signal Transduction Signaling Protein Solid Neoplasm Stomach Neoplasms Susceptibility Gene Tissues Tumor Suppressor Genes Tumor Suppressor Proteins advanced prostate cancer cancer type cell immortalization forkhead protein genetic signature improved in vivo malignant breast neoplasm malignant stomach neoplasm men novel olfactomedin outcome forecast progenitor prostate cancer cell prostate cancer progression single-cell RNA sequencing stem stem cell proliferation stem cells

项目摘要

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.

嗅觉素4（OLFM4）在正常的前列腺上皮细胞中表达，并永生化正常的人前列腺上皮细胞（RWPE1），但是这些细胞中这些细胞中OLFM4的表达细胞的同一性尚未阐明。我们在这里发现OLFM4在多个茎/祖细胞样细胞群中表达，并且经常通过执行单细胞RNA测序分析与KRT13和LY6D共表达。在功能上，与OLFM4-WILD RWPE1细胞相比，OLFM4-KNOCKOUT RWPE1细胞表现出增强的CD44+/CD49F+茎/祖细胞样细胞群的增殖增强，并中断CD24+Luminal Liminal谱系祖细胞分化。分子和信号通路研究表明，在OLFM4敲除RWPE1细胞中，Wnt/APC/MYC信号通路基因信号以及调节细胞周期的MYC靶基因的增加有所增加。这些发现确定OLFM4正在与多个茎/祖细胞标记基因共表达，并充当前列腺茎/祖细胞细胞增殖和分化的新型介体。综上所述，这些发现表明，OLFM4通过WNT/APC/MYC信号传导的多数介导，在前列腺茎/祖细胞的增殖和分化中起重要作用。