title: Hepatoma cell functions modulated by NEK2 are associated with liver cancer progression.
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.
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan, Taiwan.|Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.
authors.forename: Sheng-Ming
authors.initials: SM
authors.lastname: Wu
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan, Taiwan.
authors.forename: Syuan-Ling
authors.initials: SL
authors.lastname: Lin
authors.affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.|Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Kang-Yun
authors.initials: KY
authors.lastname: Lee
authors.affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.|Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.|School of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Hsiao-Chi
authors.initials: HC
authors.lastname: Chuang
authors.affiliation: Division of Pulmonary Medicine, Department of Internal Medicine, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan.|Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Po-Hao
authors.initials: PH
authors.lastname: Feng
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan, Taiwan.
authors.forename: Wan-Li
authors.initials: WL
authors.lastname: Cheng
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan, Taiwan.
authors.forename: Chia-Jung
authors.initials: CJ
authors.lastname: Liao
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan, Taiwan.
authors.forename: Hsiang-Cheng
authors.initials: HC
authors.lastname: Chi
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan, Taiwan.
authors.forename: Yang-Hsiang
authors.initials: YH
authors.lastname: Lin
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan, Taiwan.
authors.forename: Chung-Ying
authors.initials: CY
authors.lastname: Tsai
authors.affiliation: Cardiovascular Division, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
authors.forename: Wei-Jan
authors.initials: WJ
authors.lastname: Chen
authors.affiliation: Liver Research Center, Chang Gung Memorial Hospital, Linko, Taoyuan, Taiwan.
authors.forename: Chau-Ting
authors.initials: CT
authors.lastname: Yeh
authors.affiliation: Department of Biochemistry, College of Medicine, Chang-Gung University, Taoyuan, Taiwan.|Liver Research Center, Chang Gung Memorial Hospital, Linko, Taoyuan, Taiwan.
authors.forename: Kwang-Huei
authors.initials: KH
authors.lastname: Lin
mesh_terms: D000368:Aged; D000818:Animals; D017209:Apoptosis; D063646:Carcinogenesis; D006528:Carcinoma, Hepatocellular / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018385:Centrosome / Q000378:metabolism; D002945:Cisplatin / Q000737:chemistry; D018450:Disease Progression; D004317:Doxorubicin / Q000737:chemistry; D019008:Drug Resistance, Neoplasm; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D000072379:NIMA-Related Kinases / Q000502:physiology*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic; D011379:Prognosis; D034741:RNA, Small Interfering / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D016328:NF-kappa B; D034741:RNA, Small Interfering; D004317:Doxorubicin; C089441:NEK2 protein, human; D000072379:NIMA-Related Kinases; C490317:Nek2 protein, mouse; D002945:Cisplatin
keywords: NEK2; angiogenesis; drug resistance; hepatocellular carcinoma; metastasis