Investigating the role of stromal Wnt signaling in advanced prostate cancer
Abstract
Wnt is an important signaling pathway that is dysregulated in many types of malignancies. Genomic sequencing analysis of lethal castration-resistant prostate cancer revealed mutations of the Wnt signaling pathway in 18% of cases. Activation of Wnt signaling in prostate cancer cells induces cell proliferation, metastasis, and castration resistance. These observations support that the Wnt pathway can be a therapeutic target for advanced prostate cancer. However, our recent finding published in Cell Stem Cell, a prestigious journal, showed that the Wnt signaling in stromal cells suppresses the growth of prostate epithelial cells. This indicates that Wnt signaling plays contradictory roles in the stromal and epithelial cells. Our preliminary data demonstrated that the Wnt signaling is also present in the stromal cells in advanced prostate cancer specimens. Therefore, it is critical to investigate the role of stromal Wnt signaling in the progression of prostate cancer. Our proposed research using disease-relevant preclinical prostate cancer models will reveal the expression profile of Wnt pathway components in the stromal cells and the effects of stromal Wnt signaling activity on the progression and metastasis of advanced prostate cancer. This knowledge will help reveal whether Wnt signaling should be targeted simultaneously in both prostate tumor cells and stromal cells, and if not, how to design a therapeutic strategy that only targets Wnt signaling in the prostate cancer cells. Therefore, our proposed study will help address one of the FY19 PCRP Overarching Challenges: “Develop treatments that improve outcomes for men with lethal prostate cancer.” With my enthusiasm for biomedical science, I plan to seek a faculty position in a research-oriented institution after my postdoctoral training. Being an independent investigator, my knowledge and scientific trainings will be fully taken advantage of to understand the biology of prostate cancer, improve treatments, and eventually help cure lethal prostate cancer. This proposed research plan provides a valuable opportunity to extend my study on stromal-epithelial interaction in normal prostate development to the advanced prostate cancer progression. Under the mentorships of Drs. Li Xin and Peter Nelson, my proposed researcher development plan will qualify me for translational studies using both the animal models and clinical specimens from human patients to extend my research from understanding the basic biology of prostate cancer to improving clinical treatments. All of these will lay a solid foundation for my future career as an independent investigator for prostate cancer research.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010039
Entities
People
- Wei Xing
Organizations
- United States Army
- University of Washington