Role of WNT7B-induced noncanonical pathway in advanced prostate cancer

Dali Zheng, Keith F. Decker, Tianhua Zhou, Jianquan Chen, Zongtai Qi, Kathryn Jacobs, Katherine N. Weilbaecher, Eva Corey, Fanxin Long, Li Jia

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Advanced prostate cancer is characterized by incurable castration-resistant progression and osteoblastic bone metastasis. While androgen deprivation therapy remains the primary treatment for advanced prostate cancer, resistance inevitably develops. Importantly, mounting evidence indicates that androgen receptor (AR) signaling continues to play a critical role in the growth of advanced prostate cancer despite androgen deprivation. While the mechanisms of aberrant AR activation in advanced prostate cancer have been extensively studied, the downstream AR target genes involved in the progression of castration resistance are largely unknown. Here, we identify WNT7B as a direct AR target gene highly expressed in castration-resistant prostate cancer (CRPC) cells. Our results show that expression of WNT7B is necessary for the growth of prostate cancer cells and that this effect is enhanced under androgen-deprived conditions. Further analyses reveal that WNT7B promotes androgen-independent growth of CRPC cells likely through the activation of protein kinase C isozymes. Our results also show that prostate cancer-produced WNT7B induces osteoblast differentiation in vitro through a direct cell-cell interaction, and that WNT7B is upregulated in human prostate cancer xenografts that cause an osteoblastic reaction when grown in bone. Taken together, these results suggest that AR-regulated WNT7B signaling is critical for the growth of CRPC and development of the osteoblastic bone response characteristic of advanced prostate cancer.

Original languageEnglish
Pages (from-to)482-493
Number of pages12
JournalMolecular Cancer Research
Volume11
Issue number5
DOIs
StatePublished - May 1 2013
Externally publishedYes

Fingerprint Dive into the research topics of 'Role of WNT7B-induced noncanonical pathway in advanced prostate cancer'. Together they form a unique fingerprint.

  • Cite this

    Zheng, D., Decker, K. F., Zhou, T., Chen, J., Qi, Z., Jacobs, K., Weilbaecher, K. N., Corey, E., Long, F., & Jia, L. (2013). Role of WNT7B-induced noncanonical pathway in advanced prostate cancer. Molecular Cancer Research, 11(5), 482-493. https://doi.org/10.1158/1541-7786.MCR-12-0520