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Hepatoma cell functions modulated by NEK2 are associated with liver cancer progression
Author(s) -
Wu ShengMing,
Lin SyuanLing,
Lee KangYun,
Chuang HsiaoChi,
Feng PoHao,
Cheng WanLi,
Liao ChiaJung,
Chi HsiangCheng,
Lin YangHsiang,
Tsai ChungYing,
Chen WeiJan,
Yeh ChauTing,
Lin KwangHuei
Publication year - 2017
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30559
Subject(s) - cancer research , angiogenesis , metastasis , biology , protein kinase b , integrin linked kinase , pi3k/akt/mtor pathway , mmp2 , carcinogenesis , cell growth , tumor progression , kinase , cancer , signal transduction , microbiology and biotechnology , protein kinase a , cyclin dependent kinase 2 , genetics
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.