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

Programmed cell death protein 4 (PDCD4) has recently been shown to be involved in both transcription and translation1and 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 Twistl and leads to reduced cell growth through the down-regulation of the Twistl target gene Y-box binding protein-1 (YB-I). PDCD4 interacts with the DNA binding domain of Twistl, inhibiting its DNA binding ability and YB-I expression. Immunohistochemical analysis showed that an inverse correlation between nuclear PDCD4 and YB-I expression levels was observed in 37 clinical prostate cancer specimens. Growth suppression by PDCD4 expression was completely recovered by either Twistl or YB-I expression.Moreover, PDCD4-overexpressing cells are sensitive to cis-platin and paclitaxel but not to etoposide or 5-fluorouracil. In summary, PDCD4 negatively regulates YB-I expression via its interaction with Twistl and is involved in cancer cell growth and chemoresistance.