age - rage调控肿瘤内部pERK/Sp1/IL6通路,重编程巨噬细胞,促进肝内胆管癌进展

IF 5 2区 医学 Q2 Medicine
Juan Zhang , Biyang Jing , Xiaojian Ni , Youpei Lin , Jiaomeng Pan , MaoPei Chen , Boheng Zhang , Lan Zhang , Ningling Ge , Ruyuan Deng , Xiao Wang , Guohe Song
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引用次数: 0

摘要

肿瘤常表现为缺氧和葡萄糖摄取增强,导致糖酵解。高血糖激活信号通路诱导晚期糖基化终产物(AGEs)蛋白修饰,通过结合其受体(RAGE)促进癌症进展。在本研究中,ages处理可促进肝内胆管癌细胞(ICC)的生长、侵袭和迁移,同时增加IL-6的表达和分泌。同时,AGEs以剂量依赖性的方式刺激RAGE、特异性蛋白1 (Sp1)和细胞外信号调节激酶(ERK)磷酸化的表达。然而,这些作用被RAGE抗体阻断、RAGE敲低、ERK抑制剂U0126或sp1特异性siRNA减弱。此外,ages处理的RBE细胞上清可诱导THP-1巨噬细胞M2极化。因此,AGEs部分通过pERK/Sp1/IL-6通路和M2巨噬细胞极化促进ICC进展。这些发现强调了age - rage轴在通过pERK/Sp1/IL-6信号传导推动ICC进展中的作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
AGEs-RAGE manipulates tumor intrinsic pERK/Sp1/IL6 pathway and reprograms macrophage to promote intrahepatic cholangiocarcinoma progression
Tumors often exhibit oxygen deprivation and enhanced glucose uptake, leading to glycolysis. Advanced glycation end products (AGEs) protein modifications induced by hyperglycemia—activate signaling pathways that promote cancer progression upon binding to its receptor (RAGE). In this study, AGEs-treatment enhanced the growth, invasion and migration of intrahepatic cholangiocarcinoma cells (ICC), while increasing IL-6 expression and secretion. Meanwhile, AGEs stimulated the expression of RAGE, specificity protein 1 (Sp1), and the phosphorylation of extracellular signal-regulated kinase (ERK) in a dose-dependent manner. However, these effects were attenuated by RAGE antibody blockade, RAGE knockdown, the ERK inhibitor U0126, or Sp1-specific siRNA. Furthermore, the supernatant of AGEs-treated RBE cells induced M2 polarization of THP-1 macrophages. Thus, AGEs promote ICC progression partly through the pERK/Sp1/IL-6 pathway and M2 macrophage polarization. These findings highlight underscore the role of the AGEs-RAGE axis in driving ICC progression via pERK/Sp1/IL-6 signaling.
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来源期刊
CiteScore
8.40
自引率
2.00%
发文量
314
审稿时长
54 days
期刊介绍: Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.
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