MICAL1 stability by PlexinA1 promotes gastric cancer cell migration

Abstract

Abstract Background For metastasis to proceed, tumor cells must become mobile by modulating their cytoskeleton. MICAL1 is known as an actin cytoskeleton regulator, but the mechanisms by which it drives cancer cell migration are still unclear. Methods Immunohistochemistry assays and western blotting were used to detect the expression levels of MICAL1 in gastric cancer tissues and cells. Immunoprecipitation and immunofluorescence staining were used to detect the interactions of proteins. Wound-healing and transwell assays were performed to demonstrate the migratory function of MICAL1 in gastric cancer cells. In addition, qPCR, bioinformatics analysis, pulldown assay, ROS detection as well as western blotting were conducted to verify the mechanism of MICAL1 in gastric cancer cell migration. Results Analysis of gastric cancer tissues revealed that MICAL1 are elevated in gastric cancer tissues compared with non-tumor tissues and that its high expression is predictive of poor survival. PlexinA1 and MICAL1 were directly interact with each other. Specific inhibition of PlexinA1 accelerated MICAL1 ubiquitination and proteasome-based degradation. Furthermore, PlexinA1 positively regulates MICAL1 expression via Rac1 activation and following ROS production. Functional studies confirmed that PlexinA1 and MICAL1 facilitated gastric cancer cell migration via promoting vimentin expression. Conclusions These results indicate that PlexinA1 is a key regulator of MICAL1 stability via a Rac1/ROS dependent manner, and MICAL1 stability may be involved in promoting vimentin expression and gastric cancer cell migration.