High expression of NEK2 promotes gastric cancer progression via activating AKT signaling
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ORIGINAL ARTICLE
High expression of NEK2 promotes gastric cancer progression via activating AKT signaling Hao Wan 1 & Lin Xu 2 & Huangbin Zhang 1 & Feixiang Wu 1 & Weiqiang Zeng 1 & Taiyuan Li 1 Received: 16 May 2020 / Accepted: 10 November 2020 # University of Navarra 2020
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. Keywords NEK2 . Gastric cancer . AKT signaling pathway . Aerobic glycolysis . Autophagy
Introduction Gastric cancer is one of the most common cancers all over the world with more than 1 million new cases diagnosed every year [3]. With the recognition of certain risk factors such as salt-preserved food, low dietary fiber intake, and Helicobacter 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. * Taiyuan Li [email protected] 1
Department of General Surgery, The First Affiliated Hospital of Nanchang University, No.17 Yongwaizheng Street, Donghu District, Nanchang 330006, Jiangxi, China
2
Department of Anesthesiology, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
pylori infection, the overall occurrence of gastric cancer has decreased rapidly over the past several decades [28]. However, the incidence rate of gastric cancer remains high in Eastern Asian countries of China, Japan, and Korea, accounting for nearly 50% of all cases worldwide [19, 24, 28]. Moreover, as mos
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