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. An earlier functional study revealed that NEK2 mediates drug resistance via expression of an ABCC10 transporter. Active angiogenesis and metastasis underlie the rapid recurrence and poor survival of HCC. However, the precise roles and mechanisms of NEK2 in liver cancer progression remain largely unknown.
NEK2 expression was assayed by western blot or qRT-PCR. The function of NEK2 was determined by over-expression or depletion of the gene. In vivo matrigel plug angiogenesis assay was used to determine the influence of NEK2.
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. Results from the current study showed that NEK2 mediates tumor metastasis and angiogenesis in vivo. NEK2-mediated drug resistance was blocked by a specific PI3K inhibitor. Moreover, NEK2 mediated liver cancer cell migration via pAKT/NF-kB 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.
Clinical trial identification
Legal entity responsible for the study
Chang-Gung Memorial Hospital, Taiwan
All authors have declared no conflicts of interest.