文章：

ESM1与c-Met相互作用通过诱导血管生成促进胃癌腹膜转移

ESM1 Interacts with c-Met to Promote Gastric Cancer Peritoneal Metastasis by Inducing Angiogenesis

原文发布日期：30 December 2023

DOI: 10.3390/cancers16010194

类型: Article

开放获取: 是

英文摘要：

The peritoneum is the most common metastatic site of advanced gastric cancer and is associated with extremely poor prognosis. Endothelial-specific molecule 1 (ESM1) was found to be significantly associated with gastric cancer peritoneal metastasis (GCPM); however, the biological functions and molecular mechanisms of ESM1 in regulating GCPM remain unclear. Herein, we demonstrated that ESM1 expression was significantly upregulated in gastric cancer tissues and positively correlated with platelet endothelial cell adhesion molecule-1 (CD31) levels. Moreover, clinical validation, in in vitro and in vivo experiments, confirmed that ESM1 promoted gastric cancer angiogenesis, eventually promoting gastric cancer peritoneal metastasis. Mechanistically, ESM1 promoted tumor angiogenesis by binding to c-Met on the vascular endothelial cell membrane. In addition, our results confirmed that ESM1 upregulated VEGFA, HIF1α, and MMP9 expression and induced angiogenesis by activating the MAPK/ERK pathway. In conclusion, our findings identified the role of ESM1 in gastric cancer angiogenesis and GCPM, thus providing insights into the diagnosis and treatment of advanced gastric cancer.

摘要翻译： 

腹膜是晚期胃癌最常见的转移部位，与极差的预后密切相关。研究发现内皮特异性分子1（ESM1）与胃癌腹膜转移显著相关，但ESM1在调控胃癌腹膜转移中的生物学功能及分子机制尚不明确。本研究证实，ESM1在胃癌组织中表达显著上调，且与血小板内皮细胞黏附分子-1（CD31）水平呈正相关。通过临床验证及体内外实验发现，ESM1能够促进胃癌血管生成，最终推动胃癌腹膜转移。机制研究表明，ESM1通过与血管内皮细胞膜上的c-Met结合促进肿瘤血管生成。此外，研究结果证实ESM1通过激活MAPK/ERK通路，上调VEGFA、HIF1α和MMP9表达，从而诱导血管生成。本研究明确了ESM1在胃癌血管生成及腹膜转移中的作用，为晚期胃癌的诊断和治疗提供了新的思路。

原文链接：

ESM1 Interacts with c-Met to Promote Gastric Cancer Peritoneal Metastasis by Inducing Angiogenesis