Hepatoma cell functions modulated by NEK2 are associated with liver cancer progression |
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| Authors: | Kang‐Yun Lee Hsiao‐Chi Chuang Po‐Hao Feng Wan‐Li Cheng Chia‐Jung Liao Hsiang‐Cheng Chi Yang‐Hsiang Lin Chung‐Ying Tsai Wei‐Jan Chen Chau‐Ting Yeh Kwang‐Huei Lin |
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| Affiliation: | 1. Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan;2. Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;3. Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan;4. School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan;5. Department of Biochemistry, College of Medicine, Chang‐Gung University, Taoyuan, Taiwan;6. Cardiovascular Division, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan;7. Liver Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan |
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| Abstract: | 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. |
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| Keywords: | NEK2 drug resistance metastasis angiogenesis hepatocellular carcinoma |
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