| Nuclear receptor Nur77 is linked to the development of many types of cancer including breast cancer,colon cancer,pancreatic cancer.However,the function of Nur77 in Hepatocellular carcinoma(HCC)is still unclear.Here we found that Nur77 promotes liver cancer cell adhesion,migration and invasion through upregulating the expression of integrin β3.And Nur77 also induces downstream effectors of integrin β1,such as FAK and Paxillin.The interacton between FAK and Paxillin plays an important role in cell focal adhesion.We found that inhibition of FAK can inverse the function of Nur77 which can increase liver cancer cell migration and invasion and further testified Nur77 can mediate the downstream effectors of cell migration.HBx plays an essential role in the HCC induced by HBV.It was reported that HBx can promotes cell migration via calpain.Also reported that HBx can upregulate the transcription activation of Nur77 significantly.We have concluded that Nur77 can promote HCC matastasis and then we suppose that HBx may be the upstream of Nur77 inducing the migration and invasion in HCC.We tested the expression of HBx and Nur77 on protein level and the fact is HBx hardly affect the expression of Nur77.Interestingly,HBx can intereact with Nur77 in hepatoma cells and clinical HCC samples and they can colocate in the cell nucleus.Subsequently,we found HBx can enhance the transactivation of Nur77 and changed the expression of Nur77 downstream gene,like E-cadherin,vimentin,MMP2.On basis of the above results,we further studied how HBx regulates liver cancer cell migration and invasion.As we expected,HBx can augment HCC cell migration and invasion denpendent of Nur77.In conclusion,the research elucidates the function and mechanism of Nur77 in liver cancer metastasis.Nur77 could promote HCC cell migration and invasion through integrin β1 and we confirm that HBx affects the HCC metastasis through Nur77,which provides a new strategy for the therapy of HCC metastasis caused by HBx. |
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