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ARTICLE

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

HUNG-WEI LIN1, PEI YU LEE1, YU-SHIUAN CHANG1, MAU-SUN CHANG1,2,*
1 Institute of Biochemical Sciences, National Taiwan University, Taipei, 10617, Taiwan
2 Institute of Biological Chemistry, Academia Sinica, Taipei, 115201, Taiwan
* Corresponding Author: MAU-SUN CHANG. Email: email

Oncology Research https://doi.org/10.32604/or.2024.053791

Received 10 May 2024; Accepted 19 July 2024; Published online 09 September 2024

Abstract

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.

Keywords

Arhgap39; Hepa1-6; Hepa-1c1c7; Invasion

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