抑制雄激素受体信号通路通过上调膜联蛋白 A1 的表达促进前列腺癌细胞迁移。

Inhibition of Androgen Receptor Signaling Promotes Prostate Cancer Cell Migration via Upregulation of Annexin A1 Expression.

机构信息

Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China.

Department of Urology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China; Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an, PR China; Key Laboratory for Tumor Precision Medicine of Shaanxi Province, Xi'an, PR China.

出版信息

Arch Med Res. 2021 Feb;52(2):174-181. doi: 10.1016/j.arcmed.2020.10.005. Epub 2020 Oct 13.

DOI:10.1016/j.arcmed.2020.10.005

PMID:33059953

Abstract

BACKGROUND

Recent studies indicate that androgen deprivation therapy (ADT), the main therapeutic approach for metastatic prostate cancer (PCa), accelerates PCa invasion and metastasis. Annexin A1 (ANXA1) is a Ca-regulated phospholipid-binding protein that can promote PCa migration and invasion.

AIM OF THE STUDY

The aim of this study is to determine whether ANXA1 is regulated by ADT and participates in PCa progression after ADT, and to explore the possible mechanism of ANXA1-mediated PCa migration.

METHODS

Expression of ANXA1 and androgen receptor (AR) in PCa cell lines and tissues was detected, and the association between these two proteins were analyzed. Expression of ANXA1 was evaluated after AR knockdown or AR inhibition in PCa cell lines. Cell migration of PCa cell liness after ANXA1 knockdown or overexpression was determined by in vitro migration assay. Transcriptome analysis was used to explore the possible mechanism of ANXA1-mediated PCa migration.

RESULTS

ANXA1 expression in PCa cell lines and tissues was reversely associated with AR. In vitro studies revealed an increase in ANXA1 expression after AR knockdown or treatment with AR antagonist. Moreover, functional assays indicated that ANXA1 knockdown in PCa cells significantly inhibited cell migration, while ANXA1 overexpression in PCa cells significantly accelerated cell migration. Transcriptome analysis showed that ANXA1 regulated multiple genes involved in cell junction organization, such as CADM1, LIMCH1 and PPM1F.

CONCLUSIONS

Our results indicate that ADT might accelerate PCa metastasis via ANXA1 expression and PCa cell migration.

摘要

背景

最近的研究表明，去势治疗（ADT）作为转移性前列腺癌（PCa）的主要治疗方法，会加速 PCa 的侵袭和转移。膜联蛋白 A1（ANXA1）是一种 Ca 调节的磷脂结合蛋白，可促进 PCa 的迁移和侵袭。

目的

本研究旨在确定 ANXA1 是否受 ADT 调节，并参与 ADT 后 PCa 的进展，探讨 ANXA1 介导的 PCa 迁移的可能机制。

方法

检测 PCa 细胞系和组织中 ANXA1 和雄激素受体（AR）的表达，并分析这两种蛋白之间的关联。在 PCa 细胞系中敲低 AR 或抑制 AR 后，评估 ANXA1 的表达。通过体外迁移试验测定 PCa 细胞系中 ANXA1 敲低或过表达后细胞的迁移。通过转录组分析探讨 ANXA1 介导的 PCa 迁移的可能机制。

结果

PCa 细胞系和组织中 ANXA1 的表达与 AR 呈负相关。体外研究显示，AR 敲低或用 AR 拮抗剂处理后，ANXA1 的表达增加。此外，功能测定表明，PCa 细胞中 ANXA1 的敲低显著抑制细胞迁移，而 PCa 细胞中 ANXA1 的过表达则显著加速细胞迁移。转录组分析显示，ANXA1 调节了多个参与细胞连接组织的基因，如 CADM1、LIMCH1 和 PPM1F。