PAK4 Binds And Regulates Abi3 To Affect Invasion And Metastasis Of HCC Cells

Background Hepatocellular carcinoma(HCC)is the second leading cause of cancer death worldwide.There are about 1 million cases of liver cancer worldwide each year.In order to improve the survival rate of liver cancer patients,it is very important to study genes controlling metastasis and identify new prognostic markers and therapeutic targets.Abi3(also known as NESH)is a member of Abi family.It has Src homologous 3(SH3)domain,proline rich region(PR),and no catalytic motif.As a adptor protein,current studies show that Abi3 is likely to be an inhibiting factor for cell migration and invasion.P21 activated kinase(PAK)family,as the downstream effectors of small GTPase Cdc42 and Rac,plays a key role in cytoskeletal recombination,survival,motility and tumorigenesis.PAK4 is closely related to the progression and metastasis of cancer and may become a predictive marker and therapeutic target of cancer.In this study,HCC was used as the research model of Abi3 to clarify its potential role and downstream pathways in HCC proliferation,migration and invasion mediated by PAK4.Our results suggest that Abi3 plays a role in HCC progression and is a potentially useful molecular prognostic marker and therapeutic target.Objective To study the role of Abi3 in HCC.Study the action mode between PAK4 and Abi3;The effects of PAK4 and Abi3 on HCC invasion and metastasis were studied.Methods Select suitable HCC cell lines to steadily down-regulate Abi3,and use cell function experiment to study the effect of Abi3 lossing on HCC.The interaction between Abi3 and PAK4 was determined by immunoprecipitation,different truncated vectors of Abi3 were constructed according to the structural domain of Abi3,and the binding area was determined by immunoprecipitation.Appropriate HCC cell lines were selected for stable up-regulation of PAK4,and the effect of up-regulation of PAK4 on Abi3 and the invasion and metastasis of cell HCC cell lines were detected.Results Stable down-regulation of Abi3 in Hep3B cells can increase cell proliferation,promote non-anchored dependent growth,and increase cell migration and invasion.The SH3 domain of Abi3 and PAK4 can interact in a non-kinase-dependent manner.PAK4 can inhibit Abi3 expression and promote cell migration and invasion.Conclusion Abi3 lossing in HCC cell lines can promote tumor proliferation,migration and invasion.PAK4 binds to the SH3 domain of Abi3 in a non-kinase-dependent manner,and down-regulates Abi3 expression,promoting migration and invasion of HCC.