ADP ribosylation factor guanylate kinase 1 promotes the malignant phenotype of gastric cancer by regulating focal adhesion kinase activation

Aims: ADP ribosylation factor guanylate kinase 1 (ASAP1), a phospholipid-dependent guanosine triphosphate (GTP)ase activating protein, has been reported to be involved in the development of various malignant tumors. However, the biological function of ASAP1 in gastric cancer (GC) remains unclear. This study was to investigate its effect and the underlying mechanism for the malignant phenotype of GC. Materials and methods: The Cell Counting Kit-8 assay, flow cytometry, Transwell invasion assay, and wound-healing assay were used to assess the malignant biological behavior of GC cells with ASAP1 overexpression and knockdown. In addition, co-immunoprecipitation was used to analyze the interaction between ASAP1 and FAK in BGC823 cells, and western blotting was used to determine the effects of overexpression and knockdown of ASAP1 on FAK activity in BGC823 cells. Subsequently, functional recovery experiments were used to observe the effect of ASAP1 and FAK on the malignant phenotype of GC cells. Key findings: ASAP1 overexpression strongly promoted the malignant biological behavior of SGC7901 cells. Knockdown of ASAP1 effectively weakened the malignant biological behavior of SGC7901 and BGC823 cells. ASAP1 directly interacted with FAK to potentiate FAK activation. In addition, knockdown of FAK combined with ASAP1 overexpression significantly weakened the malignant biological behavior of GC cells, whereas overexpression of FAK combined with knockdown of ASAP1 significantly enhanced the malignant biological behavior of GC cells. Significance: ASAP1 interacted with FAK, and ASAP1 promoted the malignant phenotype of GC cells by regulating FAK activity. The specific underlying mechanism is worth further investigation.

Automated summary

The study demonstrates that overexpression of ASAP1 promotes malignant behavior in GC cells, while knockdown of ASAP1 weakens this behavior. ASAP1 interacts directly with FAK to regulate its activity, affecting the malignant phenotype of GC cells. Further investigation into the specific underlying mechanisms is warranted.