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.

Original languageEnglish
Pages (from-to)1581-1596
Number of pages16
JournalInternational Journal of Cancer
Volume140
Issue number7
DOIs
Publication statusPublished - Apr 1 2017

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Liver Neoplasms
Hepatocellular Carcinoma
Drug Resistance
Centrosome
Neoplasm Metastasis
NIMA-Related Kinases
Survival
Protein-Serine-Threonine Kinases
Growth
Matrix Metalloproteinases
Interleukin-8
Phosphatidylinositol 3-Kinases
Doxorubicin
Cisplatin
Transcriptional Activation
Cell Movement
Neoplasms
Carcinogenesis
Recurrence

Keywords

  • angiogenesis
  • drug resistance
  • hepatocellular carcinoma
  • metastasis
  • NEK2

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Hepatoma cell functions modulated by NEK2 are associated with liver cancer progression. / Wu, Sheng Ming; Lin, Syuan Ling; Lee, Kang Yun; Chuang, Hsiao Chi; Feng, Po Hao; Cheng, Wan Li; Liao, Chia Jung; Chi, Hsiang Cheng; Lin, Yang Hsiang; Tsai, Chung Ying; Chen, Wei Jan; Yeh, Chau Ting; Lin, Kwang Huei.

In: International Journal of Cancer, Vol. 140, No. 7, 01.04.2017, p. 1581-1596.

Research output: Contribution to journalArticle

Wu, SM, Lin, SL, Lee, KY, Chuang, HC, Feng, PH, Cheng, WL, Liao, CJ, Chi, HC, Lin, YH, Tsai, CY, Chen, WJ, Yeh, CT & Lin, KH 2017, 'Hepatoma cell functions modulated by NEK2 are associated with liver cancer progression', International Journal of Cancer, vol. 140, no. 7, pp. 1581-1596. https://doi.org/10.1002/ijc.30559
Wu, Sheng Ming ; Lin, Syuan Ling ; Lee, Kang Yun ; Chuang, Hsiao Chi ; Feng, Po Hao ; Cheng, Wan Li ; Liao, Chia Jung ; Chi, Hsiang Cheng ; Lin, Yang Hsiang ; Tsai, Chung Ying ; Chen, Wei Jan ; Yeh, Chau Ting ; Lin, Kwang Huei. / Hepatoma cell functions modulated by NEK2 are associated with liver cancer progression. In: International Journal of Cancer. 2017 ; Vol. 140, No. 7. pp. 1581-1596.
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AU - Cheng, Wan Li

AU - Liao, Chia Jung

AU - Chi, Hsiang Cheng

AU - Lin, Yang Hsiang

AU - Tsai, Chung Ying

AU - Chen, Wei Jan

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AU - Lin, Kwang Huei

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