Feng Wenchang, Ting Yi, Tang Xing, Liu Dan, Zhou Wen-Chao, Li Yukun, Shen Zhenyu
Cardiology Department, The Third Xiangya Hospital, Central South University, Changsha, China.
Department of Trauma Center, Zhuzhou Central Hospital, Xiangya Hospital Zhuzhou Central South University, Central South University, Zhuzhou, Hunan, China.
Heliyon. 2024 Aug 24;10(17):e36897. doi: 10.1016/j.heliyon.2024.e36897. eCollection 2024 Sep 15.
Lung adenocarcinoma (LUAD) is one of the respiratory diseases with high mortality and incidence. As an important angiogenic factor, (Endothelial cell-specific molecule 1) ESM1 plays an important role in the occurrence and development of LUAD. However, the role and molecular mechanism of ESM1 on LUAD metabolic reprogramming and angiogenesis remain unclear.
We used multiple databases to analyze the prognostic significance and potential function of ESM1 in patients with LUAD. The expression of ESM1 in LUAD cells was down-regulated/overexpressed by RNA interference, and the effects of ESM1 on the proliferation, migration, lipid metabolism and angiogenesis of LUAD cells in vitro and in vivo were analyzed using MTT, EdU, wound healing, oil red O, tubule formation, xenograft tumor model and chicken embryo allantoic model.
ESM1 is closely associated with poor prognosis in LUAD patients. ESM1 promotes LUAD proliferation, migration, fatty acid synthesis and angiogenesis. It also accelerates the proliferation, migration, lipid synthesis and tubule formation of endothelial cells in the tumor microenvironment in the form of secreted protein. Mechanically, ESM1 can promote the activation of AKT signaling pathway and up-regulate the expression of SCD1 and FASN.
Our results suggest that ESM1 promotes the proliferation, migration, lipid reprogramming, and angiogenesis of LUAD cells by activating the AKT signaling pathway, suggesting that ESM1 may be a potential therapeutic target and prognostic marker in LUAD patients.
肺腺癌（LUAD）是死亡率和发病率较高的呼吸系统疾病之一。作为一种重要的血管生成因子，内皮细胞特异性分子1（ESM1）在LUAD的发生发展中起重要作用。然而，ESM1对LUAD代谢重编程和血管生成的作用及分子机制仍不清楚。
我们使用多个数据库分析ESM1在LUAD患者中的预后意义和潜在功能。通过RNA干扰下调/上调LUAD细胞中ESM1的表达，并使用MTT、EdU、伤口愈合、油红O、小管形成、异种移植肿瘤模型和鸡胚尿囊模型分析ESM1对LUAD细胞体外和体内增殖、迁移、脂质代谢和血管生成的影响。
ESM1与LUAD患者的不良预后密切相关。ESM1促进LUAD增殖、迁移、脂肪酸合成和血管生成。它还以分泌蛋白的形式加速肿瘤微环境中内皮细胞的增殖、迁移、脂质合成和小管形成。机制上，ESM1可促进AKT信号通路的激活并上调SCD1和FASN的表达。
我们的结果表明，ESM1通过激活AKT信号通路促进LUAD细胞的增殖、迁移、脂质重编程和血管生成，提示ESM1可能是LUAD患者潜在的治疗靶点和预后标志物。
