KIR2DL4 promotes the proliferation of RCC cell associated with PI3K/Akt signaling activation

  • Life Sci. 2022 Mar 15;293:120320. doi: 10.1016/j.lfs.2022.120320.
Xiao-Fei Ding  1 ,  Jie Chen  1 ,  Huai-Lu Ma  1 ,  Yong Liang  2 ,  Yun-Fei Wang  3 ,  Hai-Tao Zhang  4 ,  Xin Li  5 ,  Guang Chen  6
Affiliations
  • 1. Department of Experimental and Clinical Medicine, Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, Taizhou, Zhejiang 318000, China.
  • 2. Institute of Tumor, School of Medicine, Taizhou University, Taizhou, Zhejiang 318000, China.
  • 3. Zhejiang ShengTing Biotechnology Co., Ltd., Taizhou, Zhejiang 318000, China.
  • 4. Department of Urology, Taizhou Municipal Hospital (Taizhou University Affiliated Hospital), Taizhou University, Taizhou, Zhejiang 318000, China.
  • 5. Department of Urology, Taizhou Central Hospital (Taizhou University Hospital), Taizhou University, Taizhou, Zhejiang 318000, China. Electronic address: [email protected].
  • 6. Department of Pharmacology, School of Medicine, Taizhou University, Taizhou, Zhejiang 318000, China. Electronic address: [email protected].
PMID: 35063466 DOI: 10.1016/j.lfs.2022.120320
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. However, its expression profiles and functions in solid tumor progression remain poorly defined.

Methods: In the present study, using bioinformatics analysis, immunohistochemistry, immunoblotting, MTT cell viability assay, soft agar colony formation assay and a human 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 and viability 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 found between parallel-controlled and Caki-1 cells overexpressing KIR2DL4 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 or lower in KIR2DL4 overexpressing or KIR2DL4 knocking-down Caki-1 cells compared with that in the parallel-controlled cells. In addition, PI3K Inhibitor wortmannin treatment and KIR2DL4-shRNA transfection further deregulated the levels of phosphorylated Akt and Caki-1 cell proliferation.

Conclusions: Our results indicate that KIR2DL4 is also expressed by RCC cells, which promotes RCC progression associated with PI3K/Akt activation.

Keywords
Killer cell immunoglobulin-like receptor 2DL4; Natural killer cells; Phosphatidylinositol-3-kinase; Protein kinase B; Renal cell carcinoma.
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