KIR2DL4 promotes the proliferation of renal cell carcinoma cells by PI3K/AKT signaling pathway activation
Abstract Background: Killer cell immunoglobulin-like receptor 2DL4 (KIR2DL4) is a transmembrane glycoprotein that is expressed by natural killer (NK) cells and certain subsets of T cells. It has been reported to serve an important role in the immune response. However, its expression profiles and function in solid tumor progression remain poorly defined.Methods: In the present study, using bioinformatics analysis, immunohistochemistry, immunoblotting, MTT assay, soft agar colony formation assay and a renal cell carcinoma (RCC) cell xenograft model in nude mice, we examined whether KIR2DL4 is expressed by RCC and its possible roles in RCC progression. Results: We confirmed that KIR2DL4 is overexpressed by RCC cells. MTT and soft agar cloning assays showed that KIR2DL4 knockdown delayed cell proliferation in RCC cell lines, Caki-1 and 769-P, in vitro. By contrast, KIR2DL4 overexpression promoted Caki-1 cell proliferation both in vitro and in vivo, which was observed in a BALB/c-nu/nu xenograft mouse model. Moreover, RNA sequencing data demonstrated that the differentially expressed genes between vector controlled and KIR2DL4-overexpressed Caki-1 cells were highly associated with cancer development, of which those related to the phosphatidylinositol-3-kinase (PI3K)/ protein kinase B (AKT) signaling pathway were particularly enriched. Immunoblotting data showed that the level of AKT phosphorylation was higher in KIR2DL4-overexpressing Caki-1 cells compared with that in the parallel-controlled cells. Conclusions: Our results indicate that KIR2DL4 is also expressed by RCC cells, which promotes RCC progression through the PI3K/AKT signaling pathway.