PKD1 Inhibits Cancer Cells Migration And Invasion Via Wnt Signaling Pathway In Vitro

BACKGROUND & OBJECTIVE: The PKD1 is the major disease-causing gene of autosomal dominant polycystic kidney disease (ADPKD) which is characterized by progressive formation of cysts in ductal organs principally in the kidneys and the liver.PC-1,which is encoded by PKD1, has a fairly wide tissue distribution, PC-1 is believed to participate in cell-cell/matrix interaction, regulation of cell proliferation, apoptosis, and cation transport, and G-protein-coupled signaling, PC-1 is thought to be a cell-cell/matrix adhesion receptor. Moreover, PC-1 is considered to be a novel member of the tumor suppressor family of proteins. This study was tying to provide direct evidence linking increased PC-1 expression to inhibited migration and invasion in cancer cells Invitro.METHODS: We established carcinoma cell model in human liver carcinoma cell line HepG2, human lung carcinoma cell line A549 and human colon carcinoma cell line SW480. Then we divided each cell line into four groups. The cells treated with PKD1 cDNA encoding PKD1 gene (therapy group), the cells treated with pcDNA3.1 group encoding null PKD1 gene (control group 2), negative control group (control group 3), Wnt inhibitor trdeated group (control group 4), respectively. The cancer cells adherence to the collagen, and the cancer cells aggregation, migration and the cancer cells invasion into the collegan was observed and photographed in three separate fields under×100 magnifications. And we also showed that polycystin-1 regulated these processes that may be at least partially through Wnt pathway by western blotting.RESULTS:①We found that cancer cells adhereto collagen 1-coated plated plates were enhanced by overexpression of PKD1 cDNA, the cells number was higher compared with other control about 0.5% (~#P<0.01) ;②We found that cancer cell aggregation was promoted by PKDl gene. Cells treated with PKDl underwent a greater aggregation as assessed by the number of aggregation platelets and by the size of the aggregation compared with the other two groups;③Cell migration assay showed that overexpression of PKD1 inhibits the migration of cancer cells Invitro. During a period of 16 hours, the negative control cells moved forward and closed the gap in the cell monolayer, however, the expression of PKD1 in the HepG2 cells resulted in a strong inhibition of migration compared with the other control cells;④The cell invasion assays revealed that the overexpression of PKD1 in cancer cells led to a decreased invasion ability to collagen. The cell number was decreased three times compared with the other control;⑤Our data suggest that the effects of PKD1 on cell adhesion and invasion may be at least partially mediated by Wnt pathway in cancer cells.CONCLUSION: Increased PC-1 expression to inhibited migration and invasion in cancer cells Invitro, suggesting the role of PKD1 as a novel member of the tumor suppressor family of genes.