RelB promotes the migration and invasion of prostate cancer DU145 cells via exosomal ICAM1 in vitro
RelB promotes the migration and invasion of prostate cancer DU145 cells via exosomal ICAM1 in vitro
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DOI：
10.1016/j.cellsig.2021.110221
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发表时间：
2022-03-01
影响因子：
4.8
通讯作者：
Guo, Feng
中科院分区：
文献类型：
--
作者：
Li, Wenjing;Xu, Jingjing;Guo, Feng
RelB赋予前列腺癌（PC）细胞攻击性。外泌体调节PC的肿瘤发生和进展。我们的目的是鉴定外泌体中的下游分子，RelB通过该下游分子增加DU 145的侵袭性。通过液相色谱-质谱联用技术从RelB基因敲低的DU145细胞中鉴定出137个上调和55个下调的外泌体蛋白。UALCAN、GeneMANIA和组织芯片分析显示，PC中细胞间粘附分子-1（ICAM-1）与RelB呈正相关，并与RelB共表达。荧光素酶报告基因检测显示RelB与ICAM 1启动子直接结合。ICAM 1过表达可增强DU 145细胞的迁移和侵袭能力。ICAM 1过表达细胞来源的exosomes（hICAM 1-exo）可增强RelB基因敲除细胞的侵袭性，尤其是迁移和侵袭能力。在机制上，hICAM 1-exo处理后，RelB敲低细胞中ICAM 1、整合素β 1、MMP 9和uPA的表达上调。外泌体ICAM 1是RelB调节的关键分子，其增加了DU 145的侵袭性。这项研究表明，通过外泌体ICAM 1的细胞间通讯是RelB促进PC进展的一种新机制。
RelB confers the aggressiveness to prostate cancer (PC) cells. Exosomes modulate the oncogenesis and progression of PC. We aimed to identify the downstream molecule in the exosomes, by which RelB increases the aggressiveness of DU145. Totally, 137 upregulated and 55 downregulated exosomal proteins were identified from RelB-knockdown DU145 cells by Liquid Chromatography-Mass Spectrometry. UALCAN, GeneMANIA and tissue microarray analysis revealed that intercellular adhesion molecule-1 (ICAM1) was positively related to and co-expressed with RelB in PC. Luciferase reporter assay revealed that RelB bound directly to the promoter of ICAM1. ICAM1 overexpression enhanced the migration and invasion abilities of DU145 cells. Exposure to exosomes derived from ICAM1 overexpressing cells (hICAM1-exo) strengthened the aggressiveness of RelBknockdown cells, especially the migration and invasion capabilities. Mechanistically, the expression of ICAM1, Integrin beta 1, MMP9 and uPA were upregulated in RelB-knockdown cells upon hICAM1-exo treatment. Exosomal ICAM1 is the key molecule regulated by RelB, which increased the aggressiveness of DU145. The study suggests that cell-cell communication via exosomal ICAM1 is a novel mechanism by which RelB promotes PC progression.