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

• 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
• 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

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.

嗅觉介导蛋白4（OLFM 4）在正常前列腺上皮细胞和永生化的正常人前列腺上皮细胞（RWPE 1）中表达，但这些群体中表达OLFM 4的细胞的身份和OLFM 4在这些细胞中的生理功能尚未阐明。我们发现OLFM 4在多个干/祖细胞样细胞群中表达，并且通过进行单细胞RNA测序分析经常与KRT 13和LY 6D共表达。在功能上，当与OLFM 4-野生型RWPE 1细胞相比时，OLFM 4-敲除RWPE 1细胞表现出增强的CD 44 +/CD 49 F+干/祖细胞样细胞群增殖和中断的CD 24+管腔谱系祖细胞分化。分子和信号通路研究显示，在OLFM 4敲除RWPE 1细胞中，WNT/APC/MYC信号通路基因签名以及调节细胞周期的MYC靶基因增加。这些发现确定OLFM 4与多个干/祖细胞标记基因共表达，并在前列腺干/祖细胞增殖和分化中充当新的介导剂。综上所述，这些发现表明OLFM 4通过主要介导WNT/APC/MYC信号传导在前列腺干/祖细胞的增殖和分化中起重要作用。