Tumor angiogenesis is an essential event for tumor growth and metastasis. It has been showed that REC8, a component of the meiotic cohesion complex, played a vital role in Epithelial-Mesenchymal Transition (EMT) in gastric cancer. However, the role of REC8 in gastric cancer angiogenesis remains to be identified. Inhibition of REC8 expression in gastric cancer cells contributed to tumor angiogenesis in the gastric cancer microenvironment. The clinical analysis demonstrated that the loss of REC8 in gastric cancer with enrichment of MVD. Depletion of REC8 expression in gastric cancer cells significantly increased tube formation of human umbilical vein endothelial cells (HUVECs), which is attributed to enhancement of vascular endothelial growth factor (VEGF) secretion caused by REC8 slicing. While addition of neutralizing antibody targeted VEGF into supernatant drastically reversed the effect of REC8 loss in gastric cancer cells on tube formation. Mechanistic analyses indicated that ablation of REC8 promotes nuclear factor-κB (NF-κB) p65 activity and its downstream gene VEGF expression, leading to tube formation. These results demonstrated a novel REC8 function that suppressed tumor angiogenesis and progression by attenuation of VEGF in gastric cancer microenvironment.

中文翻译：

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REC8通过抑制胃癌细胞中NF-κB介导的血管内皮生长因子的表达来抑制肿瘤血管生成。

肿瘤血管生成是肿瘤生长和转移的重要事件。研究表明，REC8是减数分裂内聚复合物的组成部分，在胃癌的上皮-间质转化（EMT）中起着至关重要的作用。然而，REC8在胃癌血管生成中的作用仍有待确定。REC8表达在胃癌细胞中的抑制有助于胃癌微环境中的肿瘤血管生成。临床分析表明，胃癌中RECD的丢失伴随着MVD的富集。胃癌细胞中REC8表达的耗竭显着增加了人脐静脉内皮细胞（HUVEC）的管形成，这归因于REC8切片引起的血管内皮生长因子（VEGF）分泌增加。向中清液中加入靶向中和抗体的VEGF可以显着逆转REC8丢失在胃癌细胞中对管形成的影响。机理分析表明，REC8的消融促进了核因子-κB（NF-κB）p65活性及其下游基因VEGF的表达，从而导致了管的形成。这些结果证明了新颖的REC8功能，其通过在胃癌微环境中减弱VEGF而抑制了肿瘤血管生成和进展。