The Role Of WAVE1 In K562 Leukemia Cells Invasion And Its Mechanism

WASP-family verprolin-homologous protein 1(WAVE1)is a member of the actin regulatory protein family and play an important role in regulating actin's polymerization and cytoskeleton's reorganization.Re- cently,over-expression of WAVE1 in human blood cancer cell lines was reported.In our previous researches,high level of WAVE1 was found in mononuclear cells obtained from children's bone marrow who suffered from acute leukaemia,but its role in leukaemia is still not clear.WAVE protein family was founded involved in invasion and migration of solid tumor cells.However,WAVE1 is involved in invasion and migration in leukemia cells is unclear.Super Array PCR genechip which contains 84 genes primers and expresses in many important cancer pathway was used in the study.Higher level of several genes including MMP-2,MMP-9 and Integrinβ3 were found in K562 leukaemia cells transfected with pcDNA3.1-WAVE1,those genes are believed involving in the process of leukemia's invasion.WAVE1 may have some impact on tumor's invasion.Expression of MMP-2 on mRNA and protein's level was markedly increased by transfecting pcDNA3.1-WAVE1 in K562 cells,while MMP-2's level is much lower in cells transfected with siRNA of WAVE1. Further study found that WAVE1 may promote phosphorylation of ERK1/2 in MAPK pathway through this way WAVE1 may affect the expresion of MMP-2.By using immunofluoresence,co-localization of WAVE1 and MMP-2 in cell membrane could been shown.To detect WAVE1's effect on invasion ability of K562 cells, Transwell assay was performed.Invasion ability was enhanced in cells transfected with pcDNA3.1-WAVE1 while this ability was inhibited after using siRNA of WAVE1.In conclusion,WAVE1 may involve in migration and invasion of K562 cells by regulating the expression of MMP-2 and also by coordinating with MMP-2.WAVE1 could be a novel target to inhibit leukemia cells' invasion in the future.