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ID 111804
Title Alternative
DDX31/p53変異/EGFR経路は筋層浸潤膀胱癌の多段階進展を促進する
Critical roles of DDX31-mutp53-EGFR axis in MIBC progression
Author
Ono, Masaya National Cancer Center Research Institute
Komatsu, Masato Tokushima University
Keywords
DDX31
mutant-p53
EGFR
muscle invasive bladder cancer
Content Type
Thesis or Dissertation
Description
The p53 and EGFR pathways are frequently altered in bladder cancers, 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 and enhanced mutp53 transcriptional activation, leading to migration and invasion of MIBC. Cytoplasmic DDX31 also bound EGFR and phospho-nucleolin (p-NCL) 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 anti-tumor 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.
Journal Title
Cancer Research
ISSN
00085472
15387445
NCID
AA12004911
AA00598557
Publisher
American Association for Cancer Research
Volume
78
Issue
9
Start Page
2233
End Page
2247
Published Date
2018-02-13
Remark
内容要旨・審査要旨・論文本文の公開
本論文は, 著者Kei Daizumotoの学位論文として提出され, 学位審査・授与の対象となっている。
EDB ID
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3194号
Diploma Number
甲医第1371号
Granted Date
2018-04-26
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
Institute of Advanced Medical Sciences
Medical Sciences