Wnt/Beta-Catenin, Foxa2, and CXCR4 Axis Controls Prostate Cancer Progression
Abstract
The development of metastasis to the bone is the most dangerous complication of advanced prostate cancer (PCa), frequently resulting in significant pain. Androgen deprivation therapy is the gold standard treatment for metastatic PCa patients. However, prostate tumors become resistant to hormone ablation therapy and tumors begin to grow again. The purpose of this research is to identify mechanisms that promote metastatic castrate-resistant prostate cancer progression with the ultimate goal of finding new ways to treat patients with advanced PCa. The Wnt/beta-Catenin signaling pathway is a mechanism cancer cells use to communicate with their environment and to grow after androgen deprivation. Our previous research indicates the existence of an axis of Wnt/beta-Catenin, FOXA2, and CXCR4. In this study, we investigated their functional implication in PCa. We found that Wnt/beta-Catenin signaling is active in advanced PCa. FOXA2, a downstream target of Wnt/beta-Catenin, is important for the establishment of PCa bone metastasis. Further, we found that FOXA2 regulates the expression of PTHrP and integrin alpha 1, promoting PCa bone colonization. Furthermore, we found FOXA2 sustains AR signaling after androgen deprivation, providing a mechanism for castrate-resistant growth of PCa cells. Taken together, our study revealed a critical role of Wnt/beta-Catenin signaling and FOXA2 in PCa bone metastases.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2019
- Accession Number
- AD1095964
Entities
People
- Xiuping Yu
Organizations
- Louisiana State University Health Sciences Center Shreveport