| RRC ID |
64037
|
| 著者 |
Uno M, Saitoh Y, Mochida K, Tsuruyama E, Kiyono T, Imoto I, Inazawa J, Yuasa Y, Kubota T, Yamaoka S.
|
| タイトル |
NF-κB inducing kinase, a central signaling component of the non-canonical pathway of NF-κB, contributes to ovarian cancer progression.
|
| ジャーナル |
PLoS One
|
| 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.
|
| 巻・号 |
9(2)
|
| ページ |
e88347
|
| 公開日 |
2014-1-1
|
| DOI |
10.1371/journal.pone.0088347
|
| PII |
PONE-D-13-35695
|
| PMID |
24533079
|
| PMC |
PMC3922808
|
| MeSH |
Animals
Apoptosis
Cell Adhesion
Cell Line, Tumor
Disease Progression*
Female
Gene Expression Profiling
Gene Expression Regulation, Neoplastic
Gene Silencing
Genes, Reporter
HEK293 Cells
Humans
Mice
NF-kappa B p52 Subunit / physiology
Neoplasm Transplantation
Ovarian Neoplasms / metabolism*
Protein Serine-Threonine Kinases / physiology*
RNA Interference
Signal Transduction
|
| IF |
2.74
|
| リソース情報 |
| ヒト・動物細胞 |
OMC-3(RCB0755)
JHOC-5(RCB1520) |
