Panoply™ Human NEK2 Over-expressing Stable Cell Line

Never in mitosis gene A–related kinase 2 (NEK2) has been recognized as an oncogene involved in the initiation and progression of various human cancers. Here, researchers explored the association between NEK2 and gastric cancer. They found that NEK2 overexpression is associated with the development and progression of gastric cancer, particularly in patients with larger tumors and lymph node metastases. NEK2 overexpression binds to and inhibits protein phosphatase 1 (PP1), thereby activating AKT and its downstream oncogenic pathways. Ultimately, through the AKT/HIF1α axis, glucose metabolism is reprogrammed to aerobic glycolysis, providing rapid energy for the growth of gastric cancer cells. Furthermore, the AKT/mTOR pathway inhibits autophagy activity, leading to a weakened response to treatment and enhanced survival of tumor cells. Conversely, silencing NEK2 inactivates AKT, thereby reducing aerobic glycolysis, promoting autophagic cell death, and ultimately inhibiting the growth of gastric cancer cells. All these results indicate that NEK2 promotes gastric cancer progression by activating AKT-mediated signaling pathways, which not only expands our understanding of the pathogenesis of gastric cancer but also provides new targets for clinical treatment.

To investigate the function of NEK2 in gastric cancer, researchers constructed NEK2-overexpressing gastric cancer cell lines AGS and SNU-1. The study found that the proliferation rate (Figure 1a) and colony-forming ability (Figure 1b, c) of NEK2-overexpressing cell lines were significantly enhanced, suggesting that NEK2 plays a role in promoting gastric cancer cell growth. NEK2 was initially discovered to be involved in cell cycle regulation. Recent studies have also found that NEK2 can regulate the AKT signaling pathway by directly binding to and phosphorylating protein phosphatase 1 (PP1). Therefore, researchers used immunoprecipitation to confirm the direct interaction between NEK2 and PP1 in gastric cancer cells (Figure 1d). Furthermore, elevated PP1 phosphorylation levels were also observed in NEK2-overexpressing gastric cancer cells, which was associated with increased AKT phosphorylation and activation (Figure 1e). Therefore, NEK2 overexpression in gastric cancer cells may chelate and inactivate more PP1, thereby activating downstream AKT (Figure 1f). Since the AKT-mediated signaling pathway is involved in the development and progression of various human cancers by regulating cell growth, metabolism, migration and survival, overexpression of NEK2 may promote the progression of gastric cancer by activating the AKT signaling pathway.

Figure 1. NEK2 promotes gastric cancer cell proliferation via activating AKT signaling pathway. (Wan H, et al., 2021)