Hepatoma cell functions modulated by NEK2 are associated with liver cancer progression

NEK2 (NIMA‐related expressed kinase 2) is a serine/threonine centrosomal kinase that acts as a critical regulator of centrosome structure and function. Aberrant NEK2 activities lead to failure in regulating centrosome duplication. NEK2 overexpression promotes tumorigenesis and is associated with poor prognosis in several cancers. Increased NEK2 expression during the late pathological stage has been detected in the Oncomine liver dataset and hepatocellular carcinoma (HCC) specimens. Elevated NEK2 protein is associated with poor overall survival in patients with HCC. However, the precise roles and mechanisms of NEK2 in liver cancer progression remain largely unknown. An earlier functional study revealed that NEK2 mediates drug resistance (cisplatin or lipo‐doxorubicin) via expression of an ABCC10 transporter. Active angiogenesis and metastasis underlie the rapid recurrence and poor survival of HCC. Results from the current study showed that NEK2 mediates tumor growth, metastasis and angiogenesis in vivo. NEK2‐mediated drug resistance was blocked by a specific PI3K or AKT inhibitor. Moreover, NEK2 mediated liver cancer cell migration via pAKT/NF‐κB signaling and matrix metalloproteinase (MMP) activation. Angiogenesis was induced via the same signaling pathway and IL‐8 stimulation. Our findings collectively indicate that NEK2 modulates hepatoma cell functions, including growth, drug resistance, metastasis and angiogenesis via downstream genes activation. What's new? Hepatocellular carcinoma (HCC) is an aggressive disease that tends to spread extensively within the liver, resulting in a high frequency of disease recurrence and poor survival, despite treatment. According to the present study, the invasive nature of HCC is fueled in part by NEK2, an oncogenic serine/threonine centrosomal kinase. Experiments in a hepatoma xenograft mouse model show that NEK2 overexpression contributes to tumor growth, metastasis, and angiogenesis. In hepatoma cells, NEK2 overexpression was associated with drug resistance and decreased apoptosis. Analyses of clinical HCC specimens reveal additional links between NEK2 overexpression and increased vascular invasion.