Fig. 8: ASAP1 upregulated EGFR-MAPK pathway and promotes chemotherapy resistance by activating CDC42.

A The effect of ZCL278 on the viability of WT SGC-7901 cells in response to oxaliplatin. Cell viability was measured by CCK-8. IC50 values in two different drug treatments are shown (n = 3). B WB analysis of EGFR-MAPK pathway in SGC-7901 cells expressing ASAP1-HA and partially knocked out of ASAP1. C Phalloidin staining for F-actin (red) and EBFR (green) immunofluorescence. Nuclei were counterstained with DAPI (blue). In ASAP1 ± SGC-7901 cells, the EGFR was not located on the membrane and the cytoskeleton depolymerized. In WT SGC-7901 cells treated with ZCL278, the EGFR was not located on the membrane and the cytoskeleton depolymerized. D The effect of IQGAP1 on the viability of SGC-7901-ASAP1 ± cells in response to oxaliplatin. Cell viability was measured by CCK-8. IC50 values in two different drug treatments are shown (n = 3). E The effect of EGFR on the viability of SGC-7901 cells expressing ASAP1-HA or not in response to oxaliplatin. Cell viability was measured by CCK-8. IC50 values in two different drug treatments are shown (n = 3). ns-not significant; *p < 0.05; **p < 0.01; ***p < 0.001. F A working model of ASAP1 summarizing this study. ASAP1 was highly expressed in gastric cancer, inhibits ubiquitin-mediated degradation of IQGAP1 and promotes CDC42 activation through interaction with IQGAP1. Activated CDC42 contributes to the growth and metastasis of gastric cancer cells. In addition, activated CDC42 upregulates the EGFR pathway and causes oxaliplatin resistance in gastric cancer.