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

IF 2 4区医学 Q3 ONCOLOGY

Oncology Research Pub Date : 2025-01-16 eCollection Date: 2025-01-01 DOI:10.32604/or.2024.053791

Hung-Wei Lin, Pei Yu Lee, Yu-Shiuan Chang, Mau-Sun Chang

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引用次数: 0

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.

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来源期刊

Oncology Research 医学-肿瘤学

CiteScore

4.40

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.