The Study On The Roles Of RUNX3 In Inhibiting The Migration Of Mouse Melanoma Tumor Cells B16F10 And Upregulating WGEF Expression

Cancer is one of the major disease to be a serious impact on human health and threats to human life. But, due to its high degree of complexity, so far the mechanism of tumor metastasis is still not very clear. The migration of tumor cells is the necessary precondition of tumor invasion and metastasis, but also provides the conditions for the survival and proliferation of tumor cells. Tumor cells must use their inherent ability to invade surrounding tissue and migrate through the blood vessel wall to successfully metastasis. Because of this, the ability of migration for tumor cells determines the proliferation and metastasis of tumors. Tumor cell migration is a coordinated action of the multi-step processes. These iterative steps enable cells to keep continuous migration. In these processes, the dynamic change of actin cytoskeleton plays an important role. The rearrangement of actin cytoskeleton provides the power for the distal end projecting and forward movement.Recent studies show that RUNX3 gene is a tumor suppressor gene, whose abnormal expression plays an important role in a variety of tumorigenesis and developmental defects. And, its tumor suppressor mechanism is not fully understood. In this paper, using wound healing assay, we found that RUNX3 can inhibit the migration of mouse malignant melanoma B16F10 cells and affect their cell morphology and pseudopodia. By cell counting and using inverted fluorescence microscope, we found that RUNX3 did not affect their cell proliferation and spreading. After phalloidin labelling of the cells, our data showed that RUNX3 can enhance the formation of stress fibers, and the use of RhoA inhibitors can interrupt the regulation of RUNX3 for stress fibers. The further investigation indicated that RUNX3 can upregulate the expression of guanine nucleotide exchange factor WGEF (Arhgefl9). After B16F10 cell transfection of mWGEF cDNA, then by inverted fluorescence microscope display, we found that WGEF also affected cell morphology. From the experimental results we conclude that RUNX3 might inhibit the migration of mouse malignant melanoma cells B16F10 in part by regulation of stress fiber rearrangement via upregulation of WGEF.