論文 - 詳細
| 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 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | 293(RCB1637) |