Loss of Arhgap39 facilitates cell migration and invasion in murine hepatocellular cancer cells  

作　　者：HUNG-WEI LIN PEI YU LEE YU-SHIUAN CHANG MAU-SUN CHANG 

机构地区：[1]Institute of Biochemical Sciences,National Taiwan University,Taipei,10617,Taiwan,China [2]Institute of Biological Chemistry,Academia Sinica,Taipei,115201,Taiwan,China

出　　处：《Oncology Research》2025年第2期493-503,共11页肿瘤学研究(英文)

基　　金：supported by Academia Sinica(#20020)to MSC.

摘　　要：Background:Rho GTPases are essential regulators for cellular movement and intracellular membrane trafficking.Their enzymatic activities fluctuate between active GTP-bound and inactive GDP-bound states regulated by GTPase activating proteins(GAPs)and guanine nucleotide exchange factors(GEFs).Arhgap39/Vilse/Porf-2 is a newly identified GAP.The role of Arhgap39 in migration and invasion has not been addressed thoroughly.Methods:The Arhgap39 gene was knocked out by Crispr-Cas9 gene editing in mouse Hepa1-6 and Hepa-1c1c7 cells to analyze the impact of Arhgap39 depletion on migration and invasion.Results:Loss of Arhgap39 noticeably increased the migration and invasive potential.Purified Arhgap39 recombinant protein facilitated the hydrolysis of GTP in RhoA and Rac1 in vitro.RNA-seq analysis revealed that matrix metalloproteinase 13(MMP13)and Laminin subunit beta 1(LAMB1)were increased in Arhgap39^(^(-/-))cells.We further crossed Arhgap39fl/fl with KrasLSL-G12D and p53fl/fl mice under the control of albumin-Cre recombinase to induce the spontaneous development of hepatocellular carcinomas.Intriguingly,the expression levels of MMP13 and the overall survival in Alb-Cre_KrasLSL-G12D_p53fl/fl_Arhgap39fl/fl(KPA)mice were comparable to control Alb-Cre_KrasLSL-G12D_p53fl/fl(KP)mice.The cell migration and invasion of KPA mice were also similar to those of control KP mice.Conclusion:Arhgap39 loss could modulate the migration and invasion in some hepatocellular cancer cells,but not in those isolated from KPA mice.

关 键 词：Arhgap39 Hepa1-6 Hepa-1c1c7 INVASION 

分 类 号：R735.7[医药卫生—肿瘤]