RelB-mediated EMT activation promotesbone metastasis of prostate cancer

5^th World Congress on Cancer Therapy

September 28-30, 2015 Atlanta, USA

Yong Xu1,Fang Fang2, Chi Wang3, William H St. Clair2 and Daret K St. Clair3

1Department of Oncology, Nanjing First Hospital, Nanjing Medical University, China
2Department of Radiation Medicine
3Markey Cancer Center, University of Kentucky, USA

Scientific Tracks Abstracts: J Cancer Sci Ther

Abstract :

The NF-KB signaling pathway is well-known to be critical for cancer development; our previous studies demonstrated that the RelB-based NF-KB alternative pathway is essential for tumorigenesis of prostate cancer. Here, we show that RelB contributes to bone metastasis of prostate cancer through an EMT-activating process. High constitutive nuclear levels of RelB were observed in human prostate cancer tissues with high Gleason scores. Up-regulation of RelB in prostate cancer cells led to cell invasion and migration, which was mediated by activation ofSnail I and Twist I. ChIP revealed that RelBbindsto NF-KB enhancer elements located at the 5â��-flanking regions of both Snail I and Twist I genes, which interact with Sp1-based promoters for transcriptional activation of the genes. In addition, the high levels of RelB also increased cell mineralization that was correlated to up-regulation of the bone formation relating protein, S100A4. The RelB-mediated aggressiveness of prostate cancer cells through Snail I- and Twist I-activated PI3K-AKT pathway, which was induced by TNF�±, but suppressed by an anticancer agent, parthenolide. These results suggest that the activation of NF-KB alternative pathway enhances metastasis of prostate cancer cells by activation of the EMT process.

Biography :

Email: yxu0@uky.edu