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Role of WNT7B-induced noncanonical pathway in advanced prostate cancer

Dali Zheng1, Keith F Decker, Tianhua Zhou

  • 1Center for Pharmacogenomics, Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.

Molecular Cancer Research : MCR
|February 7, 2013
PubMed

Insights

WNT7B is a key gene in advanced prostate cancer growth and bone metastasis. Targeting this androgen receptor-regulated pathway may offer new treatments for castration-resistant prostate cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • Advanced prostate cancer often becomes castration-resistant, continuing to grow despite androgen deprivation therapy.
  • Androgen receptor (AR) signaling remains crucial for advanced prostate cancer growth, even without androgens.
  • Downstream AR target genes driving castration resistance are not well understood.

Purpose of the Study:

  • To identify novel androgen receptor (AR) target genes involved in castration-resistant prostate cancer (CRPC) progression.
  • To investigate the role of WNT7B in CRPC growth and osteoblastic bone metastasis.

Main Methods:

  • Gene expression analysis in CRPC cells.
  • Functional assays to assess WNT7B's role in cell growth under androgen-deprived conditions.
  • In vitro studies on WNT7B-induced osteoblast differentiation.
  • Analysis of WNT7B expression in prostate cancer xenografts.

Main Results:

  • WNT7B was identified as a direct AR target gene highly expressed in CRPC cells.
  • WNT7B expression is essential for prostate cancer cell growth, particularly under androgen deprivation.
  • WNT7B promotes androgen-independent CRPC growth, potentially via protein kinase C activation.
  • Prostate cancer-derived WNT7B induces osteoblast differentiation in vitro and is upregulated in bone metastatic xenografts.

Conclusions:

  • AR-regulated WNT7B signaling is critical for CRPC growth.
  • WNT7B plays a significant role in the development of osteoblastic bone responses in advanced prostate cancer.
  • Targeting WNT7B may represent a therapeutic strategy for advanced prostate cancer with bone metastasis.

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