| RRC ID |
69193
|
| 著者 |
Wu S, Kasim V, Kano MR, Tanaka S, Ohba S, Miura Y, Miyata K, Liu X, Matsuhashi A, Chung UI, Yang L, Kataoka K, Nishiyama N, Miyagishi M.
|
| タイトル |
Transcription factor YY1 contributes to tumor growth by stabilizing hypoxia factor HIF-1α in a p53-independent manner.
|
| ジャーナル |
Cancer Res
|
| Abstract |
In response to hypoxic stress, hypoxia-inducible factor (HIF)-1α is a critical transcription factor regulating fundamental cellular processes, and its elevated expression level and activity are associated with poor outcomes in most malignancies. The transcription factor Yin Yang 1 (YY1) is an important negative regulator of the tumor suppressor factor p53. However, the role of YY1 under tumor hypoxic condition is poorly understood. Herein, we show that inhibition of YY1 reduced the accumulation of HIF-1α and its activity under hypoxic condition, and consequently downregulated the expression of HIF-1α target genes. Interestingly, our results revealed that the downregulation of HIF-1α by inhibiting YY1 is p53-independent. Functionally, the in vivo experiments revealed that inhibition of YY1 significantly suppressed growth of metastatic cancer cells and lung colonization and also attenuated angiogenesis in a p53-null tumor. Collectively, our findings unraveled a novel mechanism by which YY1 inhibition disrupts hypoxia-stimulated HIF-1α stabilization in a p53-independent manner. Therefore, YY1 inhibition could be considered as a potential tumor therapeutic strategy to give consistent clinical outcomes independent of p53 status.
|
| 巻・号 |
73(6)
|
| ページ |
1787-99
|
| 公開日 |
2013-3-15
|
| DOI |
10.1158/0008-5472.CAN-12-0366
|
| PII |
0008-5472.CAN-12-0366
|
| PMID |
23328582
|
| MeSH |
Cell Division / physiology*
Cell Line, Tumor
Gene Silencing
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / genetics
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
Tumor Suppressor Protein p53 / physiology*
YY1 Transcription Factor / physiology*
|
| IF |
9.727
|
| リソース情報 |
| ヒト・動物細胞 |
Saos-2(RCB0428) |
