| RRC ID |
77029
|
| 著者 |
Daizumoto K, Yoshimaru T, Matsushita Y, Fukawa T, Uehara H, Ono M, Komatsu M, Kanayama HO, Katagiri T.
|
| タイトル |
A DDX31/Mutant-p53/EGFR Axis Promotes Multistep Progression of Muscle-Invasive Bladder Cancer.
|
| ジャーナル |
Cancer Res
|
| Abstract |
The p53 and EGFR pathways are frequently altered in bladder cancer, yet their contributions to its progression remain elusive. Here we report that DEAD box polypeptide 31 (DDX31) plays a critical role in the multistep progression of muscle-invasive bladder cancer (MIBC) through its sequential interactions with mutant p53 (mutp53) and EGFR. In early MIBC cells, nuclear DDX31-bound mutp53/SP1 enhanced mutp53 transcriptional activation, leading to migration and invasion of MIBC. Cytoplasmic DDX31 also bound EGFR and phospho-nucleolin in advanced MIBC, leading to EGFR-Akt signaling activation. High expression of both cytoplasmic DDX31 and p53 proteins correlated with poor prognosis in patients with MIBC, and blocking the DDX31/NCL interaction resulted in downregulation of EGFR/Akt signaling, eliciting an in vivo antitumor effect against bladder cancer. These findings reveal that DDX31 cooperates with mutp53 and EGFR to promote progression of MIBC, and inhibition of DDX31/NCL formation may lead to potential treatment strategies for advanced MIBC.Significance: DDX31 cooperates with mutp53 and EGFR to promote progression of muscle invasive bladder cancer. Cancer Res; 78(9); 2233-47. ©2018 AACR.
|
| 巻・号 |
78(9)
|
| ページ |
2233-2247
|
| 公開日 |
2018-5-1
|
| DOI |
10.1158/0008-5472.CAN-17-2528
|
| PII |
0008-5472.CAN-17-2528
|
| PMID |
29440146
|
| MeSH |
Animals
Biomarkers, Tumor
Cell Line, Tumor
DEAD-box RNA Helicases / metabolism*
Disease Models, Animal
Disease Progression
ErbB Receptors / metabolism*
Gene Expression Regulation, Neoplastic
Humans
Immunohistochemistry
Kaplan-Meier Estimate
Mice
Mutation
Neoplasm Invasiveness
Prognosis
Protein Binding
Transcription, Genetic
Tumor Suppressor Protein p53 / genetics*
Tumor Suppressor Protein p53 / metabolism*
Urinary Bladder Neoplasms / genetics*
Urinary Bladder Neoplasms / metabolism*
Urinary Bladder Neoplasms / mortality
Urinary Bladder Neoplasms / pathology
|
| IF |
9.727
|
| リソース情報 |
| ヒト・動物細胞 |
293(RCB1637) |
