Format

Send to

Choose Destination
Cancer Res. 2018 May 1;78(9):2233-2247. doi: 10.1158/0008-5472.CAN-17-2528. Epub 2018 Feb 13.

A DDX31/Mutant-p53/EGFR Axis Promotes Multistep Progression of Muscle-Invasive Bladder Cancer.

Author information

1
Division of Genome Medicine, Institute for Genome Research, Tokushima University, Tokushima, Japan.
2
Department of Urology, Tokushima University Graduate School of Biomedical Sciences, Tokushima, Japan.
3
Division of Pathology, Tokushima University Hospital, Tokushima, Japan.
4
Department of Clinical Proteomics, National Cancer Center Research Institute, Tokyo, Japan.
5
Division of Genome Medicine, Institute for Genome Research, Tokushima University, Tokushima, Japan. tkatagi@genome.tokushima-u.ac.jp.

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.

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center