5th World Congress on Cancer Therapy
Nanjing First Hospital, Nanjing Medical University, China
Title: RelB-mediated EMT activation promotesbone metastasis of prostate cancer
Biography: Yong Xu
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 5’-fl anking 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. Th e RelB-mediated aggressiveness of prostate cancer cells through Snail I- and Twist I-activated PI3K-AKT pathway, which was induced by TNFα, but suppressed by an anticancer agent, parthenolide. Th ese results suggest that the activation of NF-KB alternative pathway enhances metastasis of prostate cancer cells by activation of the EMT process.