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High expression of NEK2 promotes gastric cancer progression via activating AKT signaling

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Abstract

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. However, our knowledge is still lacking in regard to the function of NEK2 in gastric cancer, the most common cancer in Eastern Asia associated with poor prognosis. Therefore, in the present study, we investigated the association of NEK2 with gastric cancer. We found that the development of gastric cancer is associated with NEK2 overexpression, particularly in patients with large tumor size and lymph node metastasis. We also provided evidence that NEK2 overexpression binds to and inhibits protein phosphatase 1 (PP1), which subsequently activates AKT and the downstream oncogenic pathways. As a result, via AKT/HIF1α axis, the glucose metabolism is reprogrammed towards aerobic glycolysis to provide rapid energy for the growth of gastric cancer cells. Moreover, the autophagic activity is suppressed via AKT/mTOR axis, leading to impaired response to cancer treatment and enhanced cell survival. In contrast, inactivating AKT by NEK2 silencing decreases aerobic glycolysis and promotes autophagic cell death, which eventually inhibits the growth of gastric cancer cell. All these results revealed that NEK2 promotes gastric cancer progression via activating AKT-mediated signaling pathways, which expanded our knowledge on gastric cancer pathogenesis and also provided novel target for clinical treatment.

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Authors and Affiliations

  1. Department of General Surgery, The First Affiliated Hospital of Nanchang University, No.17 Yongwaizheng Street, Donghu District, Nanchang, 330006, Jiangxi, China

    Hao Wan, Huangbin Zhang, Feixiang Wu, Weiqiang Zeng & Taiyuan Li

  2. Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China

    Lin Xu

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  1. Hao Wan
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Contributions

HW and TL designed the study and wrote the manuscript. HW, LX, HZ, and WZ performed the experiment. HW, WZ, and TL analyzed the data and interpreted the results.

Corresponding author

Correspondence to Taiyuan Li.

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The authors declare that they have no conflict of interest.

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This study was approved by the institutional ethical review committee of the First Affiliated Hospital of Nanchang University (Ref # 20100520). All the procedures involving human subjects were in accordance with the Declaration of Helsinki in 1964.

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Written informed consent was obtained from a legally authorized representative(s) for anonymized patient information to be published in this article. All the patients signed written informed consent.

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Key points

• NEK2 is overexpressed in gastric cancer and correlated with disease progression.

• NEK2 promotes gastric cancer progression via activating the AKT signaling network.

• NEK2 favors AKT-mediated aerobic glycolysis to support gastric cancer cell growth.

• NEK2 facilitates gastric cancer cell survival via AKT-mediated autophagy inhibition.

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Wan, H., Xu, L., Zhang, H. et al. High expression of NEK2 promotes gastric cancer progression via activating AKT signaling. J Physiol Biochem 77, 25–34 (2021). https://doi.org/10.1007/s13105-020-00776-8

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  • DOI: https://doi.org/10.1007/s13105-020-00776-8

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