TY  - EJOU
AU  - LIN, HUNG-WEI 
AU  - LEE, PEI YU 
AU  - CHANG, YU-SHIUAN 
AU  - CHANG, MAU-SUN 

TI  - Loss of Arhgap39 facilitates cell migration and invasion in murine hepatocellular cancer cells
T2  - Oncology Research

PY  - 2025
VL  - 33
IS  - 2
SN  - 1555-3906

AB  -  <b>Background:</b> 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. <b>Methods:</b> 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. <b>Results:</b> Loss of Arhgap39 noticeably increased the migration and invasive potential. Purified Arhgap39 recombinant protein facilitated the hydrolysis of GTP in RhoA and Rac1 <i>in vitro</i>. RNA-seq analysis revealed that matrix metalloproteinase 13 (MMP13) and Laminin subunit beta 1 (LAMB1) were increased in Arhgap39<sup>−/−</sup> 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. <b>Conclusion:</b> Arhgap39 loss could modulate the migration and invasion in some hepatocellular cancer cells, but not in those isolated from KPA mice.
KW  - Arhgap39; Hepa1-6; Hepa-1c1c7; Invasion

DO  - 10.32604/or.2024.053791