Programmed cell death protein 4 down-regulates Y-box binding protein-1 expression via a direct interaction with Twist1 to suppress cancer cell growth

Masaki Shiota; Hiroto Izumi; Akihide Tanimoto; Mayu Takahashi; Naoya Miyamoto; Eiji Kashiwagi; Akihiko Kidani; Gen Hirano; Daisuke Masubuchi; Yasushi Fukunaka; Yoshihiro Yasuniwa; Seiji Naito; Shigeru Nishizawa; Yasuyuki Sasaguri; Kimitoshi Kohno

doi:10.1158/0008-5472.CAN-08-2334

Programmed cell death protein 4 down-regulates Y-box binding protein-1 expression via a direct interaction with Twist1 to suppress cancer cell growth

Cancer Res. 2009 Apr 1;69(7):3148-56. doi: 10.1158/0008-5472.CAN-08-2334. Epub 2009 Mar 24.

Authors

Masaki Shiota¹, Hiroto Izumi, Akihide Tanimoto, Mayu Takahashi, Naoya Miyamoto, Eiji Kashiwagi, Akihiko Kidani, Gen Hirano, Daisuke Masubuchi, Yasushi Fukunaka, Yoshihiro Yasuniwa, Seiji Naito, Shigeru Nishizawa, Yasuyuki Sasaguri, Kimitoshi Kohno

Affiliation

¹ Department of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, Yahatanishi-ku, Kitakyushu, Japan.

PMID: 19318582
DOI: 10.1158/0008-5472.CAN-08-2334

Abstract

Programmed cell death protein 4 (PDCD4) has recently been shown to be involved in both transcription and translation, and to regulate cell growth. However, the mechanisms underlying PDCD4 function are not well understood. In this study, we show that PDCD4 interacts directly with the transcription factor Twist1 and leads to reduced cell growth through the down-regulation of the Twist1 target gene Y-box binding protein-1 (YB-1). PDCD4 interacts with the DNA binding domain of Twist1, inhibiting its DNA binding ability and YB-1 expression. Immunohistochemical analysis showed that an inverse correlation between nuclear PDCD4 and YB-1 expression levels was observed in 37 clinical prostate cancer specimens. Growth suppression by PDCD4 expression was completely recovered by either Twist1 or YB-1 expression. Moreover, PDCD4-overexpressing cells are sensitive to cisplatin and paclitaxel but not to etoposide or 5-fluorouracil. In summary, PDCD4 negatively regulates YB-1 expression via its interaction with Twist1 and is involved in cancer cell growth and chemoresistance.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Apoptosis Regulatory Proteins / biosynthesis
Apoptosis Regulatory Proteins / genetics
Apoptosis Regulatory Proteins / metabolism*
Cell Growth Processes / physiology
Cell Line, Tumor
Cisplatin / pharmacology
Down-Regulation
Glioma / drug therapy
Glioma / genetics
Glioma / metabolism*
Glioma / pathology
Humans
Male
Nuclear Proteins / antagonists & inhibitors
Nuclear Proteins / genetics
Nuclear Proteins / metabolism*
Paclitaxel / pharmacology
Prostatic Neoplasms / drug therapy
Prostatic Neoplasms / genetics
Prostatic Neoplasms / metabolism*
Prostatic Neoplasms / pathology
RNA-Binding Proteins / biosynthesis
RNA-Binding Proteins / genetics
RNA-Binding Proteins / metabolism*
Transcription, Genetic
Transfection
Twist-Related Protein 1 / antagonists & inhibitors
Twist-Related Protein 1 / genetics
Twist-Related Protein 1 / metabolism*
Y-Box-Binding Protein 1 / biosynthesis*
Y-Box-Binding Protein 1 / genetics

Substances

Apoptosis Regulatory Proteins
Nuclear Proteins
PDCD4 protein, human
RNA-Binding Proteins
TWIST1 protein, human
Twist-Related Protein 1
Y-Box-Binding Protein 1
Paclitaxel
Cisplatin