Wnt/Beta-Catenin, Foxa2, and CXCR4 Axis Controls Prostate Cancer Progression
Annual rept. 1 Jul 2012-30 Jun 2013
VANDERBILT UNIV MEDICAL CENTER NASHVILLE TN
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Wntbeta-Catenin signaling and associated target genes are implicated in the establishment of bone metastasis and in the development of castration resistant prostate cancer. Our previous studies have shown that Foxa2 is a Wntbeta-catenin target gene in prostate. Our preliminary study suggest a Wnt Foxa2 CXCR4 axis that is involved in PCa bone metastasis, and activation of this axis provides survival mechanisms for PCa cells following androgen deprivation. The hypothesis is that the Wntbeta-catenin activation of Foxa2 and CXCR4 promotes progression to CRPCa and facilitates bone colonization by PCa cells, and that targeting this axis will provide a novel treatment for PCa bone metastasis and relapse after androgen ablation. In the past one year, our effort mainly focused on addressing if active Wntbeta-Catenin signaling induces Foxa and CXCR4 to promote androgen independent prostate cancer cell growth if knocking down Foxa2 in prostate cancer cells impairs their growth in the bone and to characterize 22Rv1 s growth in the bones.
- Anatomy and Physiology
- Medicine and Medical Research