RASAL2通过调控AKT/β-catenin信号通路促进胰腺癌细胞的血管生成拟态  

RASAL2 promotes pancreatic cancer vasculogenic mimicry through AKT/β-catenin pathway

作　　者：杨宝 马非白 钱伟琨 周灿灿[1] 王铮[1] 岳阳阳[1] YANG Bao;MA Feibai;QIAN Weikun;ZHOU Cancan;WANG Zheng;YUE Yangyang(Department of Hepatobiliary Surgery,The First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061,Shaanxi Province,China)

机构地区：[1]西安交通大学第一附属医院肝胆外科,陕西西安710061

出　　处：《肿瘤》2024年第11期1104-1115,共12页Tumor

基　　金：国家自然科学基金资助项目(82103563)

摘　　要：目的:探究RASAL2在胰腺癌细胞血管生成拟态中的作用,并初步探讨可能的分子作用机制。方法:利用临床蛋白质组学肿瘤分析联盟(clinical proteomic tumor analysis consortium, CPTAC)数据库分析RASAL2在胰腺癌中的表达情况,并采用免疫组织化学法检测胰腺癌及癌旁组织中RASAL2、β-catenin及Vimentin蛋白的表达情况。在胰腺癌细胞系中利用慢病毒感染敲低与过表达RASAL2后,对沉默RASAL2表达的胰腺癌细胞进行转录组二代测序,采用血管生成拟态实验检测RASAL2对胰腺癌细胞血管生成能力的影响;通过实时荧光定量PCR及蛋白质印迹法检测研究RASAL2促进胰腺癌血管生成拟态的分子作用机制。结果:CPTAC数据库分析结果显示,与正常胰腺组织相比,胰腺癌组织中RASAL2蛋白的表达水平明显升高。免疫组织化学法检测结果显示,RASAL2在胰腺癌组织中的表达水平上调,β-catenin及Vimentin在胰腺癌组织中的表达水平也明显上调。转录组二代测序结果显示,RASAL2可能参与了细胞间连接及黏附的生物学行为。在胰腺癌细胞PANC-1中敲低RASAL2表达后,AKT/β-catenin信号通路相关蛋白表达水平下降,血管生成拟态相关蛋白表达水平下降,血管生成拟态结构形成受到抑制;在胰腺癌细胞BxPC-3中过表达RASAL2后,AKT/β-catenin信号通路相关蛋白表达水平上升,血管生成拟态相关蛋白表达水平上升,促进血管生成拟态形成。结论:RASAL2对胰腺癌细胞血管生成拟态的影响与AKT/β-catenin信号通路有关。Objective:To investigate the role of RASAL2 in vasculogenic mimicry in pancreatic cancer cells and to preliminarily explore the potential molecular mechanisms involved.Methods:The clinical proteomic tumor analysis consortium(CPTAC)database was used to analyze the expression of RASAL2 in pancreatic cancer,and immunohistochemical method was used to detect the expression of RASAL2,β-catenin and Vimentin in pancreatic cancer and adjacent tissues.In the pancreatic cancer cell line,after lentivirus infection knockdown and overexpression of RASAL2,transcriptome sequencing was performed on pancreatic cancer cells silencing RASAL2 expression,and vasculogenic mimicry experiment was used to detect the effect of RASAL2 on angiogenesis of pancreatic cancer cells;The molecular mechanism of RASAL2 promoting vasculogenic mimicry in pancreatic cancer was studied by real-time fluorescent quantitative PCR and Western blotting detection.Results:The analysis results of CPTAC database showed that the expression level of RASAL2 protein in pancreatic cancer tissue was significantly higher than that in normal pancreatic tissue.Immunohistochemical test results showed that the expression of RASAL2 in pancreatic cancer tissue was up-regulated,and the expression ofβ-catenin and Vimentin in pancreatic cancer tissue was also significantly up-regulated.The second-generation transcriptome sequencing results showed that RASAL2 may be involved in the biological behavior of intercellular connections and adhesion.After knocking down RASAL2 expression in pancreatic cancer cell PANC-1,the expression level of AKT/β-catenin signaling pathway related proteins and vasculogenic mimicry related proteins decreased,and the formation of vasculogenic mimicry structure was inhibited;After overexpression of RASAL2 in pancreatic cancer cell BxPC-3,the expression level of AKT/β-catenin signaling pathway related proteins and vasculogenic mimicry related proteins increased,promoting the formation of vasculogenic mimicry.Conclusion:The effect of RASAL2 on vasculog

关 键 词：胰腺癌 RASAL2 Β-CATENIN 血管生成拟态 

分 类 号：R735.9[医药卫生—肿瘤]