血管生成
癌症研究
血管内皮生长因子A
车站3
染色质免疫沉淀
化学
生物
血管内皮生长因子
细胞生物学
信号转导
发起人
基因表达
生物化学
基因
血管内皮生长因子受体
作者
Lingnan He,Anqi Feng,Hui Guo,Haohao Huang,Qingchun Deng,Ende Zhao,Ming Yang
出处
期刊:Gastric Cancer
[Springer Nature]
日期:2022-01-30
卷期号:25 (3): 527-541
被引量:16
标识
DOI:10.1007/s10120-022-01279-9
摘要
Increasing evidence indicates that leucine-rich-alpha-2-glycoprotein 1 (LRG1) is associated with multiple malignancies, but whether it participates in gastric cancer (GC) angiogenesis remains unclear.The expression levels of LRG1 were assessed in GC samples. Endothelial tube formation analysis, HUVEC migration assay, chorioallantoic membrane assay (CAM), and xenograft tumor model were used to investigate the effect of LRG1 on angiogenesis in gastric cancer. The involvement of activating transcription factor 3 (ATF3) was analyzed by chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assay. Western blot and enzyme-linked immunosorbent assay were performed to measure the SRC/STAT3/VEGFA pathway.LRG1 was overexpressed in GC tissues and associated with cancer angiogenesis. In addition, LRG1 markedly promoted GC cell proliferation in vitro and in vivo. Moreover, overexpression of LRG1 could stimulate GC angiogenesis in vitro and in vivo. Then, we identified ATF3 promotes the transcription of LRG1 and is a positive regulator of angiogenesis. Additionally, LRG1 could activate VEGFA expression via the SRC/STAT3/ VEGFA pathway in GC cells, thus contributing to the angiogenesis of GC.The present study suggests LRG1 plays a crucial role in the regulation of angiogenesis in GC and could be a potential therapeutic target for GC.
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