title: NF-κB inducing kinase, a central signaling component of the non-canonical pathway of NF-κB, contributes to ovarian cancer progression.
abstract: Ovarian cancer is one of the leading causes of female death and the development of novel therapeutic approaches is urgently required. Nuclear factor-κB (NF-κB) is constitutively activated in several types of cancer including ovarian cancer and is known to support the survival of cancer cells. However, molecular mechanisms of persistent activation of NF-κB in ovarian cancer remain largely unknown. We report here that, in addition to the previously reported canonical activation, NF-κB is activated through the noncanonical pathway in ovarian cancer cells. RNA interference-mediated silencing of NF-κB inducing kinase (NIK), a central regulator of the noncanonical pathway, reduced the NF-κB2/p52 DNA binding activity and NF-κB-dependent reporter gene expression as well as NF-κB target gene expression. Notably, anchorage-dependent and -independent cell growth was impaired in NIK-depleted cells. Depletion of NIK also suppressed tumor formation in the nude mouse xenograft assay. These results indicate that NIK plays a key role in constitutive NF-κB activation and the progression of ovarian cancer cells and suggest that NIK represents an attractive therapeutic target for ovarian cancer.
authors.affiliation: Department of Comprehensive Reproductive Medicine, Tokyo Medical and Dental University, Tokyo, Japan ; Department of Molecular Virology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masaya
authors.initials: M
authors.lastname: Uno
authors.affiliation: Department of Molecular Virology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Saitoh
authors.affiliation: Department of Molecular Virology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Kanako
authors.initials: K
authors.lastname: Mochida
authors.affiliation: Department of Molecular Virology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Eri
authors.initials: E
authors.lastname: Tsuruyama
authors.affiliation: Virology Division, National Cancer Center Research Institute, Tokyo, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Kiyono
authors.affiliation: Department of Human Genetics, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima, Japan.
authors.forename: Issei
authors.initials: I
authors.lastname: Imoto
authors.affiliation: Department of Molecular Cytogenetics, Medical Research Institute and School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Johji
authors.initials: J
authors.lastname: Inazawa
authors.affiliation: Department of Molecular Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Yuasa
authors.affiliation: Department of Comprehensive Reproductive Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Toshiro
authors.initials: T
authors.lastname: Kubota
authors.affiliation: Department of Molecular Virology, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Shoji
authors.initials: S
authors.lastname: Yamaoka
mesh_terms: D000818:Animals; D017209:Apoptosis; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D017930:Genes, Reporter; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D052003:NF-kappa B p52 Subunit / Q000502:physiology; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D034622:RNA Interference; D015398:Signal Transduction; D000097782:NF-kappaB-Inducing Kinase
chemical_list: D052003:NF-kappa B p52 Subunit; D017346:Protein Serine-Threonine Kinases; D000097782:NF-kappaB-Inducing Kinase; C498206:NFKB2 protein, human